Pub Date : 2018-08-01DOI: 10.15406/MOJDDT.2018.02.00053
M. Malik
Job performance is considered as a multi dimensional concept describing the extent to which employees fulfill their responsibilities by using their creativity productivity and problem solving skills The present study was designed to assess the job performance of pharmacists working in different fields in twin cities of Pakistan A descriptive cross sectional study design was to assess the job performance of pharmacists working in different fields in twin cities i e Islamabad Federal Capital and Rawalpindi Twin City of Pakistan Sample size was calculated to be pharmacists to achieve confidence level with margin of error The performance of these selected respondents was evaluated by using Performance Evaluation Questionnaire PEQ requested to be filled by their respective reporting managers After data collection data was cleaned coded and analyzed using SPSS version Results showed that creativity was found above average among pharmacists with mean score plusmn job responsibility plusmn and management skills plusmn were also above average The overall job performance plusmn of pharmacists was also found adequate The results of the present study concluded that of pharmacists was above average Although the pharmacists were creative responsible and possessed managerial skills but still these expertise rsquo s needs to be further enhanced through extensive training and continuous professional development programs
{"title":"Can creativity, responsibility and skills guarantee better job performance of pharmacists? a cross‒sectional study from Pakistan","authors":"M. Malik","doi":"10.15406/MOJDDT.2018.02.00053","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00053","url":null,"abstract":"Job performance is considered as a multi dimensional concept describing the extent to which employees fulfill their responsibilities by using their creativity productivity and problem solving skills The present study was designed to assess the job performance of pharmacists working in different fields in twin cities of Pakistan A descriptive cross sectional study design was to assess the job performance of pharmacists working in different fields in twin cities i e Islamabad Federal Capital and Rawalpindi Twin City of Pakistan Sample size was calculated to be pharmacists to achieve confidence level with margin of error The performance of these selected respondents was evaluated by using Performance Evaluation Questionnaire PEQ requested to be filled by their respective reporting managers After data collection data was cleaned coded and analyzed using SPSS version Results showed that creativity was found above average among pharmacists with mean score plusmn job responsibility plusmn and management skills plusmn were also above average The overall job performance plusmn of pharmacists was also found adequate The results of the present study concluded that of pharmacists was above average Although the pharmacists were creative responsible and possessed managerial skills but still these expertise rsquo s needs to be further enhanced through extensive training and continuous professional development programs","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76207505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-08-01DOI: 10.15406/MOJDDT.2018.02.00052
Z. Iqbal, Amjid Khan, Nabeela Niaz
Most of the newly invented active pharmaceutical ingredients APIs are poor water soluble and dissolution rate is the limiting step in bioavailability from compressed solid dosage forms Objective of the study was to elucidate the effect of hydrophilic carriers on dissolution rate of poor water soluble drug and utilization of co grinded Clarithromycin in preparation of tablets by direct compression Intrinsic dissolution rate of Clarithromycin was determined according to United States Pharmacopeia USP using rotating disk method Hydrophilic carrier micro crystalline cellulose was applied in varying ratios and drug to carrier ratio by weight for enhancement of dissolution rate of Clarithromycin by co grinding technique Co grinded Clarithromycin was prepared by compressing lubricated physical mixture blend of Clarithromycin and micro crystalline cellulose to slugs followed by granulation Tablets containing co grinded Clarithromycin were prepared by direct compression technique and evaluated for various official and unofficial parameters at pre compression and post compression level The prepared tablets were compared with marketed tablets in terms of physical parameters mechanical strength disintegration behavior and in vitro drug release Dissolution profiles of both types of the tablets were compared on the basis of maximum drug release dissimilarity factor f similarity factor f and dissolution efficiency Clarithromycin is a class II drug with poor water solubility Its intrinsic dissolution rate is very low mg cm min In comparison to intrinsic dissolution rate significant increase in dissolution rate of Clarithromycin was observed by co grinding with hydrophilic carriers Dissolution rate of Clarithromycin enhanced with concentration of hydrophilic carrier and maximum increase was observed at drug to carrier ratio by weight By further increasing ratio of the carrier resulted in decrease in dissolution rate due to cushioning effect Tablets containing co grinded Clarithromycin showed better dissolution profile compared with marketed tablets In comparison with marketed tablets maximum drug release in min Q plusmn Q plusmn Q plusmn and dissolution efficiency were higher for tablets containing co grinded Clarithromycin Dissolution rate of poor water soluble drug Clarithromycin can be enhanced by co grinding with hydrophilic carrier micro crystalline cellulose Co grinding is an environment friendly technique that can be applied for enhancement of dissolution rate of poor water soluble APIs irrespective of nature and dose
{"title":"Evaluation of the effect of co‒grinding on dissolution rate of poor water soluble drug (clarithromycin)","authors":"Z. Iqbal, Amjid Khan, Nabeela Niaz","doi":"10.15406/MOJDDT.2018.02.00052","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00052","url":null,"abstract":"Most of the newly invented active pharmaceutical ingredients APIs are poor water soluble and dissolution rate is the limiting step in bioavailability from compressed solid dosage forms Objective of the study was to elucidate the effect of hydrophilic carriers on dissolution rate of poor water soluble drug and utilization of co grinded Clarithromycin in preparation of tablets by direct compression Intrinsic dissolution rate of Clarithromycin was determined according to United States Pharmacopeia USP using rotating disk method Hydrophilic carrier micro crystalline cellulose was applied in varying ratios and drug to carrier ratio by weight for enhancement of dissolution rate of Clarithromycin by co grinding technique Co grinded Clarithromycin was prepared by compressing lubricated physical mixture blend of Clarithromycin and micro crystalline cellulose to slugs followed by granulation Tablets containing co grinded Clarithromycin were prepared by direct compression technique and evaluated for various official and unofficial parameters at pre compression and post compression level The prepared tablets were compared with marketed tablets in terms of physical parameters mechanical strength disintegration behavior and in vitro drug release Dissolution profiles of both types of the tablets were compared on the basis of maximum drug release dissimilarity factor f similarity factor f and dissolution efficiency Clarithromycin is a class II drug with poor water solubility Its intrinsic dissolution rate is very low mg cm min In comparison to intrinsic dissolution rate significant increase in dissolution rate of Clarithromycin was observed by co grinding with hydrophilic carriers Dissolution rate of Clarithromycin enhanced with concentration of hydrophilic carrier and maximum increase was observed at drug to carrier ratio by weight By further increasing ratio of the carrier resulted in decrease in dissolution rate due to cushioning effect Tablets containing co grinded Clarithromycin showed better dissolution profile compared with marketed tablets In comparison with marketed tablets maximum drug release in min Q plusmn Q plusmn Q plusmn and dissolution efficiency were higher for tablets containing co grinded Clarithromycin Dissolution rate of poor water soluble drug Clarithromycin can be enhanced by co grinding with hydrophilic carrier micro crystalline cellulose Co grinding is an environment friendly technique that can be applied for enhancement of dissolution rate of poor water soluble APIs irrespective of nature and dose","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76413724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.15406/mojddt.2018.02.00047
H. Dureja
{"title":"Chromatographic methods used for characterization of boswellic acids","authors":"H. Dureja","doi":"10.15406/mojddt.2018.02.00047","DOIUrl":"https://doi.org/10.15406/mojddt.2018.02.00047","url":null,"abstract":"","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81430419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-09DOI: 10.15406/MOJDDT.2018.02.00046
D. Mahapatra, K. Dadure, Ruchi Shivhare
Murraya koenigii L. (family: Rutaceae), also known as Indian curry plant is having ethnopharmacological importance.1 The plant parts (root, leaf, and stem bark) are known to have several biological activities like anti‒helminthic, carminative, stomachic, febrifuge, astringent purgative, etc.2 These activities are a function of the phytoconstituents of carbazole scaffolds like euchrestine B, mahanine, O‒ methylmurrayamine A, bismurrayafoline, murrayanine, bismahanine, koenimbine, mahaninebine, isomahanine, O‒methylmahanine, bispyrayafoline, and mahaninebicine which in scientific studies over the years have represented potent anti‒ulcerogenic, anti‒ bacterial, anti‒oxidant, anti‒fungal, immunomodulation, etc.3 Murrayanine is the most imperative, most active, and highly explored phytoconstituent which have been studied by our research group over the years.4 A chalcone derivative, designated by us as “Murrayanine‒ Chalcone” was synthesized,5 and a number of heterocyclic derivatives (oxadiazole,6 thiazole,7 thiadiazole,8 hydantoin,9 benzodiazepine,10 pyrazole,11 benzoxazepine,12 pyrimidine,13 benzothiazepine,14 isoxazole,15 3,4‒methylenedioxy,16 and phthalimide,17 were fabricated in order to amplify the biological activities (anti‒diabetic, anti‒inflammatory, anti‒oxidant, anti‒anxiety, antibacterial, anti‒ convulsant, and anti‒fungal) by using the most common strategy ‘hybridization’. Chalcone or 1,3‒diphenyl‒2E‒propene‒1‒one comprises of a benzylideneacetophenone scaffold where the two aromatic nuclei joined by a three carbon α, β unsaturated carbonyl bridge.18 This scaffold is easy to synthesize and exhibit diverse options for substitution and their profound capability to exhibit diverse biological activities such as hypoglycemic, hypolipidemic, antihypertensive, anti‒platelet, anti‒arrhythmic, anti‒obesity, anti‒ infective, etc.19‒21 Chalcones have tremendous potential of exhibiting anti‒inflammatory activity and the development of a chalcone analog of murrayanine may have the perspectives of better anti‒inflammatory activity than the parent moiety itself.22 In the present research, hydroxylated derivatives of murrayanine‒chalcone were rationally designed and synthesized from murrayanine (1) and hydroxylated acetophenones (2a‒c) to obtain hydroxylated derivatives using the previously reported protocol and to explore the anti‒inflammatory potential using carrageenan‒induced paw edema method. In addition to it, the establishment of the possible structure‒activity‒relationship (SAR) was done, which will be beneficial for the medicinal chemists in further designing target modulators.
{"title":"Exploring the site‒specific influence of hydroxyl group in ring‒B of murrayanine‒chalcone on edema reducing potential","authors":"D. Mahapatra, K. Dadure, Ruchi Shivhare","doi":"10.15406/MOJDDT.2018.02.00046","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00046","url":null,"abstract":"Murraya koenigii L. (family: Rutaceae), also known as Indian curry plant is having ethnopharmacological importance.1 The plant parts (root, leaf, and stem bark) are known to have several biological activities like anti‒helminthic, carminative, stomachic, febrifuge, astringent purgative, etc.2 These activities are a function of the phytoconstituents of carbazole scaffolds like euchrestine B, mahanine, O‒ methylmurrayamine A, bismurrayafoline, murrayanine, bismahanine, koenimbine, mahaninebine, isomahanine, O‒methylmahanine, bispyrayafoline, and mahaninebicine which in scientific studies over the years have represented potent anti‒ulcerogenic, anti‒ bacterial, anti‒oxidant, anti‒fungal, immunomodulation, etc.3 Murrayanine is the most imperative, most active, and highly explored phytoconstituent which have been studied by our research group over the years.4 A chalcone derivative, designated by us as “Murrayanine‒ Chalcone” was synthesized,5 and a number of heterocyclic derivatives (oxadiazole,6 thiazole,7 thiadiazole,8 hydantoin,9 benzodiazepine,10 pyrazole,11 benzoxazepine,12 pyrimidine,13 benzothiazepine,14 isoxazole,15 3,4‒methylenedioxy,16 and phthalimide,17 were fabricated in order to amplify the biological activities (anti‒diabetic, anti‒inflammatory, anti‒oxidant, anti‒anxiety, antibacterial, anti‒ convulsant, and anti‒fungal) by using the most common strategy ‘hybridization’. Chalcone or 1,3‒diphenyl‒2E‒propene‒1‒one comprises of a benzylideneacetophenone scaffold where the two aromatic nuclei joined by a three carbon α, β unsaturated carbonyl bridge.18 This scaffold is easy to synthesize and exhibit diverse options for substitution and their profound capability to exhibit diverse biological activities such as hypoglycemic, hypolipidemic, antihypertensive, anti‒platelet, anti‒arrhythmic, anti‒obesity, anti‒ infective, etc.19‒21 Chalcones have tremendous potential of exhibiting anti‒inflammatory activity and the development of a chalcone analog of murrayanine may have the perspectives of better anti‒inflammatory activity than the parent moiety itself.22 In the present research, hydroxylated derivatives of murrayanine‒chalcone were rationally designed and synthesized from murrayanine (1) and hydroxylated acetophenones (2a‒c) to obtain hydroxylated derivatives using the previously reported protocol and to explore the anti‒inflammatory potential using carrageenan‒induced paw edema method. In addition to it, the establishment of the possible structure‒activity‒relationship (SAR) was done, which will be beneficial for the medicinal chemists in further designing target modulators.","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87234991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-06DOI: 10.15406/MOJDDT.2018.02.00045
E. Lattmann, S. Russell, Mankaran Singh, R. Narayanan, P. Balaram, P. Lattmann
Background: Cholecystokinin and gastrin are endocrine growths factors for certain tumours and CCK1 R and CCK2R receptors are ideal molecular targets for novel smart chemo‒ therapeutics with a beneficial overall profile due to their anxiolytic and antidepressant properties. Lung cancers are fuelled by gastrin and therefore, selective gastrin (CCK2 R) antagonists are ideal experimental drug candidates. Objective: Synthesis and evaluation of novel CCK antagonists, most preferred CCK2 / gastrin selective for the treatment of lung cancers. Methods: A fast and efficient synthesis of hydroxy‒pyrrolones in 2 steps from renewable biomass was performed. After initial radiolabelled receptor binding studies with hot CCK8, subsequent in vitro evaluation with isolated duodenum preparations confirmed CCK antagonism. Cell based studies using the MTT assay provided a candidate for in vivo xenograft models with nude mice. Rational drug design was supported by molecular modelling experiments. Results: Potent and selective CCK antagonists were prepared as stable crystalline materials in high yields. Gastrin antagonists were in vitro active on isolated tissue preparations and inhibited breast, colon and lung cancer cell lines in vitro with IC50 to 45nM for the privileged hydroxyl‒pyrrolone lead structure in the MTT assay for human cancer cell lines. PNB‒101, a fluorinated 5‒hydroxy‒5‒aryl‒pyrrol‒2‒one, gave up to 80% inhibition of tumour growths by oral administration in athymic mice transplanted with the human lung cancer cell line H727. Conclusion: PNB‒101 is a potential chemotherapeutic agent for CCK‒gastrin related cancers and entered preclinical development.
{"title":"N‒substituted 5‒hydroxy‒pyrrol‒2‒ones based cholecystokinin‒2 antagonists as experimental anticancer agents for the treatment of lung cancer","authors":"E. Lattmann, S. Russell, Mankaran Singh, R. Narayanan, P. Balaram, P. Lattmann","doi":"10.15406/MOJDDT.2018.02.00045","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00045","url":null,"abstract":"Background: Cholecystokinin and gastrin are endocrine growths factors for certain tumours and CCK1 R and CCK2R receptors are ideal molecular targets for novel smart chemo‒ therapeutics with a beneficial overall profile due to their anxiolytic and antidepressant properties. Lung cancers are fuelled by gastrin and therefore, selective gastrin (CCK2 R) antagonists are ideal experimental drug candidates. Objective: Synthesis and evaluation of novel CCK antagonists, most preferred CCK2 / gastrin selective for the treatment of lung cancers. Methods: A fast and efficient synthesis of hydroxy‒pyrrolones in 2 steps from renewable biomass was performed. After initial radiolabelled receptor binding studies with hot CCK8, subsequent in vitro evaluation with isolated duodenum preparations confirmed CCK antagonism. Cell based studies using the MTT assay provided a candidate for in vivo xenograft models with nude mice. Rational drug design was supported by molecular modelling experiments. Results: Potent and selective CCK antagonists were prepared as stable crystalline materials in high yields. Gastrin antagonists were in vitro active on isolated tissue preparations and inhibited breast, colon and lung cancer cell lines in vitro with IC50 to 45nM for the privileged hydroxyl‒pyrrolone lead structure in the MTT assay for human cancer cell lines. PNB‒101, a fluorinated 5‒hydroxy‒5‒aryl‒pyrrol‒2‒one, gave up to 80% inhibition of tumour growths by oral administration in athymic mice transplanted with the human lung cancer cell line H727. Conclusion: PNB‒101 is a potential chemotherapeutic agent for CCK‒gastrin related cancers and entered preclinical development.","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81912712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-02DOI: 10.15406/MOJDDT.2018.02.00049
V. Ashwlayan, Saurabh Nimesh
On May first Nipah Virus NiV outbreak was reported from Kozhikode district of Kerala and Mallapuram district of South India There is high risk of NiV outbreak to individual as well as community NiV is classed across the world as a bio safety level BSL hazards Emerging zoonotic risk grade RG Hendra and Nipah viruses cause severe and often lethal respiratory illness encephalitis particularly in sows boars and human and have public impact on human health fever aches tiredness chills amp nervous signs twitching trembling muscle fasciculation spasms muscle weak spot convulsions and death Zoonotic diseases transfer to human being from animals NiV can infect a huge variety of species Transmission of NiV from human being to human being has been observed They are associated with high risk group of life threatening disease in human and or animals Treatment is restrained to supportive care Because NiV encephalitis can be transmitted from one person to another person standard infection control practices and proper barrier nursing techniques are important to prevent nosocomial transmission infections For handling RG Nipah virus there is a requirement for a laboratory with extensive BSL high level containment that includes practices BSL plus controlled access safety equipment rsquo s Biological Safety Cabinet full body air supplied positive pressure and personnel suit and facilities BSL plus dedicated air and exhaust decontamination procedures for exit separate building Biological safety cabinets use high efficiency particulate air HEPA filters in their exhaust and or supply systems A Power Air Purifying Respirator PAPR or tight fitting goggles and N respirator should be worn for high risk aerosol generating procedures The therapeutic use of a neutralizing human monoclonal antibody targeting the Nipah G glycoprotein has experimentally been evaluated in the post exposure therapy in the ferret model and found to be of benefit Additional efforts focused on surveillance and awareness will assist save future outbreaks
{"title":"Nipah virus: an update","authors":"V. Ashwlayan, Saurabh Nimesh","doi":"10.15406/MOJDDT.2018.02.00049","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00049","url":null,"abstract":"On May first Nipah Virus NiV outbreak was reported from Kozhikode district of Kerala and Mallapuram district of South India There is high risk of NiV outbreak to individual as well as community NiV is classed across the world as a bio safety level BSL hazards Emerging zoonotic risk grade RG Hendra and Nipah viruses cause severe and often lethal respiratory illness encephalitis particularly in sows boars and human and have public impact on human health fever aches tiredness chills amp nervous signs twitching trembling muscle fasciculation spasms muscle weak spot convulsions and death Zoonotic diseases transfer to human being from animals NiV can infect a huge variety of species Transmission of NiV from human being to human being has been observed They are associated with high risk group of life threatening disease in human and or animals Treatment is restrained to supportive care Because NiV encephalitis can be transmitted from one person to another person standard infection control practices and proper barrier nursing techniques are important to prevent nosocomial transmission infections For handling RG Nipah virus there is a requirement for a laboratory with extensive BSL high level containment that includes practices BSL plus controlled access safety equipment rsquo s Biological Safety Cabinet full body air supplied positive pressure and personnel suit and facilities BSL plus dedicated air and exhaust decontamination procedures for exit separate building Biological safety cabinets use high efficiency particulate air HEPA filters in their exhaust and or supply systems A Power Air Purifying Respirator PAPR or tight fitting goggles and N respirator should be worn for high risk aerosol generating procedures The therapeutic use of a neutralizing human monoclonal antibody targeting the Nipah G glycoprotein has experimentally been evaluated in the post exposure therapy in the ferret model and found to be of benefit Additional efforts focused on surveillance and awareness will assist save future outbreaks","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83923701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-02DOI: 10.15406/MOJDDT.2018.02.00050
Vikas Pahal, U. Devi, K. Dadhich
Plant based naturally occurring phytochemicals have great inhibitory potential against various pathogenic bacteria but the mechanism of inhibition and the essential cell molecules to which they bind and inhibit remain unclear and unexplored so far In the present study we examined the effect of secondary metabolites from C officinalis both in vitro and in silico to decrypt the probable pathway of inhibition In in vitro experiments Staphylococcus aureus was used to evaluate the antibacterial potential of secondary metabolites present in different organic extracts of C officinalis using agar well diffusion and XTT colorimetric methods In in silico experiments important C officinalis secondary metabolites viz Alpha cadinol Scopoletin Esculetin and Quercetin were docked against essential enzymes of bacteria like Peptide deformylase Gamma hemolysins Undecaprenyl pyrophosphate synthase and DNA primases to assess their antibacterial potential using AutoDock Vina The enzyme ligand interaction of docked complexes was further analyzed by Molecular Dynamics Simulation technique using GROMACS As per in vitro results methanolic extract was found to be the most promising extract having highest antibacterial potential where the mg ml concentration of the extract was found to completely inhibit the bacterial growth whereas for pure Quercetin the complete inhibition was achieved at mg ml concentration MIC was observed to be and mg ml with methanolic and pure Quercetin extracts respectively Whereas MBC values were found to be and mg ml for methanolic extract and Quercetin respectively As per in silico results Quercetin was found to be the only secondary metabolite which strongly inhibited three essential enzymes of S aureus like Peptide deformylase Undecaprenyl pyrophosphate synthase and DNA primases enzymes which resulted in the inhibition of post translation cell wall biosynthesis and initiation of replication pathways respectively As Quercetin was found in methanolic extract of C officinalis we have successfully demonstrated that C officinalis has great potential to inhibit the growth of S aureus
{"title":"Quercetin, a secondary metabolite present in methanolic extract of Calendula officinalis, is a potent inhibitor of peptide deformylase, undecaprenyl pyrophosphate synthase and DNA primase enzymes of Staphylococcus aureus: an in vitro and in silico result analysis","authors":"Vikas Pahal, U. Devi, K. Dadhich","doi":"10.15406/MOJDDT.2018.02.00050","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00050","url":null,"abstract":"Plant based naturally occurring phytochemicals have great inhibitory potential against various pathogenic bacteria but the mechanism of inhibition and the essential cell molecules to which they bind and inhibit remain unclear and unexplored so far In the present study we examined the effect of secondary metabolites from C officinalis both in vitro and in silico to decrypt the probable pathway of inhibition In in vitro experiments Staphylococcus aureus was used to evaluate the antibacterial potential of secondary metabolites present in different organic extracts of C officinalis using agar well diffusion and XTT colorimetric methods In in silico experiments important C officinalis secondary metabolites viz Alpha cadinol Scopoletin Esculetin and Quercetin were docked against essential enzymes of bacteria like Peptide deformylase Gamma hemolysins Undecaprenyl pyrophosphate synthase and DNA primases to assess their antibacterial potential using AutoDock Vina The enzyme ligand interaction of docked complexes was further analyzed by Molecular Dynamics Simulation technique using GROMACS As per in vitro results methanolic extract was found to be the most promising extract having highest antibacterial potential where the mg ml concentration of the extract was found to completely inhibit the bacterial growth whereas for pure Quercetin the complete inhibition was achieved at mg ml concentration MIC was observed to be and mg ml with methanolic and pure Quercetin extracts respectively Whereas MBC values were found to be and mg ml for methanolic extract and Quercetin respectively As per in silico results Quercetin was found to be the only secondary metabolite which strongly inhibited three essential enzymes of S aureus like Peptide deformylase Undecaprenyl pyrophosphate synthase and DNA primases enzymes which resulted in the inhibition of post translation cell wall biosynthesis and initiation of replication pathways respectively As Quercetin was found in methanolic extract of C officinalis we have successfully demonstrated that C officinalis has great potential to inhibit the growth of S aureus","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86811720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01DOI: 10.15406/MOJDDT.2018.02.00044
S. Shilpi, Roshni Shivvedi, Ekta Gurnany, Sonal Dixit, K. Khatri, D. Dwivedi
Treatment of liver cancer and other diseases are a challenging task for the current researchers in the pharmaceutical field There are some physiological barriers like RES uptake opsonization and first pass metabolism of therapeutics present that make drug therapy more complex Generally conventional cancer therapy approaches give low response rate or remain un success due to multi drug resistance MDR high clearance rate severe adverse effect due to unwanted drug distribution and in adequate concentration reached in cancer cells Therefore it is a need to develop novel strategies which will target drug molecule specific to affected liver cells In the current era of research and development various approaches have been utilized to improve the drug delivery and drug targeting The new targeting approaches are based on the use of targeting ligands which can conjugate with nanocarrier or with drug molecules These conjugates systems are accumulate passively or actively This review focus on some liver cancer cells specific targeting ligands such as manos phosphate asialoglycoprotein galactoside lactobionic acid PDGF antibodies aptamers avimers which have been utilized to target cancer cell after conjugation with the therapeutic system This review also describes the novel targeting approaches including latest targeting molecules and targeted drug delivery system used for the treatment of liver cancer
{"title":"Drug targeting strategies for liver cancer and other liver diseases","authors":"S. Shilpi, Roshni Shivvedi, Ekta Gurnany, Sonal Dixit, K. Khatri, D. Dwivedi","doi":"10.15406/MOJDDT.2018.02.00044","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00044","url":null,"abstract":"Treatment of liver cancer and other diseases are a challenging task for the current researchers in the pharmaceutical field There are some physiological barriers like RES uptake opsonization and first pass metabolism of therapeutics present that make drug therapy more complex Generally conventional cancer therapy approaches give low response rate or remain un success due to multi drug resistance MDR high clearance rate severe adverse effect due to unwanted drug distribution and in adequate concentration reached in cancer cells Therefore it is a need to develop novel strategies which will target drug molecule specific to affected liver cells In the current era of research and development various approaches have been utilized to improve the drug delivery and drug targeting The new targeting approaches are based on the use of targeting ligands which can conjugate with nanocarrier or with drug molecules These conjugates systems are accumulate passively or actively This review focus on some liver cancer cells specific targeting ligands such as manos phosphate asialoglycoprotein galactoside lactobionic acid PDGF antibodies aptamers avimers which have been utilized to target cancer cell after conjugation with the therapeutic system This review also describes the novel targeting approaches including latest targeting molecules and targeted drug delivery system used for the treatment of liver cancer","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74542704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01DOI: 10.15406/MOJDDT.2018.02.00048
A. Kushwah, Prabhjot Kaur, Thippeswamy Boreddy Shivanandappa
Tectona grandis TG plant belonging to family Verbenaceae it is medicinally reported and claims to cure various diseases in Indian traditional system Ayurveda and in folklore The purpose of this study is to examine the methanol extract of Tectona grandis leaves TGME in Streptozotocin STZ induced diabetic neuropathy in rat Initially acute oral toxicity study of TGME was carried out in rats to evaluate the dose for animal study STZ mg kg was used to induce diabetes in rats TGME was given orally dose of and mg kg to normal and diabetic rats from initiate th to th weeks total days Blood collection for estimation of glucose level biochemical parameters and behavioural parameters were assessed initially up to th week every nd week interval At the end of study after th week rats were sacrificed for estimation brain tissue estimations and histopathology of rat paw skin was also carried out In acute oral toxicity study result TGME do not cause any toxicity or death in animals Diabetic rat rsquo s significant increase in serum glucose and other biochemical parameters as well as mechanical allodynia was indicates hyperalgesia after weeks of diabetes induction Brain tissue estimations revealed increase in lipid peroxidation LPO level a decrease in antioxidant parameters and histopathology study of paw skins of rat rsquo s intraepidermal nerve fiber density was decreased in diabetic neuropathy STZ treated group Administration of dose of and mg kg of TGME significantly P lt decreased blood glucose level in normal and diabetic rats A dose of mg kg significantly P lt and P lt increases the tail withdrawal latency with hot and cold water tail immersion tests respectively Both the doses of TGME significantly increase the level of glutathione GSH and lower the levels of LPO catalase CAT and superoxide dismutase SOD Histopathology study of paw skin of rat intraepidermal nerve fiber density was increased as a result of drug administration The results concluded that TGME possesses potential to combat glucose hypolipidemic effect and scavenge free radicals in diseases associated with oxidative stress suggests its role in preventing diabetes related complications
Tectona茅TG属于家庭马鞭草科植物是报道的药用价值和索赔治愈各种疾病在印度阿育吠陀传统系统和民俗本研究的目的是检查Tectona茅叶的甲醇提取物在链脲霉素TGME STZ诱导糖尿病神经病变最初在大鼠急性口服毒性研究TGME在老鼠进行动物研究评价剂量STZ毫克公斤用于诱导糖尿病大鼠TGME口服剂量毫克公斤正常和糖尿病大鼠从启动th - th周总天采血血糖水平估计生化参数和行为参数评估最初th星期每nd周间隔th星期后在研究结束时,老鼠牺牲估计脑组织估计和皮肤组织病理学的鼠爪也在急性口服毒性研究结果TGME不会导致任何糖尿病大鼠动物中毒或死亡糖尿病诱导后大鼠足部皮肤脂质过氧化LPO水平升高，抗氧化参数降低，组织病理学研究显示糖尿病神经病变STZ治疗组表皮内神经纤维密度降低，给药剂量和mg / kg TGME显著降低plt血糖水平在正常和糖尿病大鼠显著剂量毫克公斤P lt和P lt增加尾部撤军延迟分别与热水和冷水的尾巴浸试验的剂量TGME显著提高谷胱甘肽,谷胱甘肽水平降低的水平提供法律服务外包的过氧化氢酶和超氧化物歧化酶SOD的组织病理学研究猫爪老鼠的皮肤表皮内的神经纤维密度增加的药品管理局认为TGME拥有的结果在与氧化应激相关的疾病中，潜在的对抗低血糖和清除自由基的作用表明它在预防糖尿病相关并发症中的作用
{"title":"Effect of methanolic extracts of Tectona grandis linn leaves on diabetic neuropathy in streptozotocin‒induced diabetic rats","authors":"A. Kushwah, Prabhjot Kaur, Thippeswamy Boreddy Shivanandappa","doi":"10.15406/MOJDDT.2018.02.00048","DOIUrl":"https://doi.org/10.15406/MOJDDT.2018.02.00048","url":null,"abstract":"Tectona grandis TG plant belonging to family Verbenaceae it is medicinally reported and claims to cure various diseases in Indian traditional system Ayurveda and in folklore The purpose of this study is to examine the methanol extract of Tectona grandis leaves TGME in Streptozotocin STZ induced diabetic neuropathy in rat Initially acute oral toxicity study of TGME was carried out in rats to evaluate the dose for animal study STZ mg kg was used to induce diabetes in rats TGME was given orally dose of and mg kg to normal and diabetic rats from initiate th to th weeks total days Blood collection for estimation of glucose level biochemical parameters and behavioural parameters were assessed initially up to th week every nd week interval At the end of study after th week rats were sacrificed for estimation brain tissue estimations and histopathology of rat paw skin was also carried out In acute oral toxicity study result TGME do not cause any toxicity or death in animals Diabetic rat rsquo s significant increase in serum glucose and other biochemical parameters as well as mechanical allodynia was indicates hyperalgesia after weeks of diabetes induction Brain tissue estimations revealed increase in lipid peroxidation LPO level a decrease in antioxidant parameters and histopathology study of paw skins of rat rsquo s intraepidermal nerve fiber density was decreased in diabetic neuropathy STZ treated group Administration of dose of and mg kg of TGME significantly P lt decreased blood glucose level in normal and diabetic rats A dose of mg kg significantly P lt and P lt increases the tail withdrawal latency with hot and cold water tail immersion tests respectively Both the doses of TGME significantly increase the level of glutathione GSH and lower the levels of LPO catalase CAT and superoxide dismutase SOD Histopathology study of paw skin of rat intraepidermal nerve fiber density was increased as a result of drug administration The results concluded that TGME possesses potential to combat glucose hypolipidemic effect and scavenge free radicals in diseases associated with oxidative stress suggests its role in preventing diabetes related complications","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87193507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-22DOI: 10.15406/mojddt.2018.02.00043
R. Gunda, Prasada Rao Manchineni, D. Dhachinamoorthi
Enteral route is the most comfortable, extensively used route of administration for both prompt delivery systems and new drug delivery systems. Tablets are the most famous solid formulations available in the market and are preferred by patients and physicians alike. In case of treatment of chronic disease conditions, conventional release formulations are required to be administered in frequent manner and therefore shows patient non‒adherence to prescription.1 However, ingestion of majority of drugs shows first pass effect and/or first pass hepatic metabolism presystemic elimination by gastrointestinal degradation as a result of which low systemic bioavailability and shorter duration of action and development of non‒active or toxic transformed products.2 The objective of a sustained release (SR) dosage form is to maintain CSS levels for prolonged period. Systems that are designated as modified release/timed release can also be considered as attempts at achieving prolonged drug delivery.3‒6 SR formulations offers greater reduction in dosing frequency in comparison with immediate release formulations.7 SR formulations afford advantage over prompt release formulations by optimising biopharmaceutical, pharmacokinetic and pharmacodynamic properties of drug. The utilization of macromolecules like polymers in modulating the rate of drug release has turn to an essential tool in the product development of pharmaceutical formulations. Numerous reports over many years reveals that they play key role in the release of drugs from dosage form for various drugs.8 Natural polymers preferred primarily because they were economic, high drug holding capacity, high thermal stability, non‒carcinogenicity, mucoadhesivity, biodegradable, biocompatible, broad regulatory acceptance and ease of compression. Various gums and mucilages were used for the development of sustained release formulations in such as gums (xanthan, tragacanth, guar), pectin, alginates etc. cellulose derivatives such as HPC, HPMC, CMC, SCMC have been widely used as release retardants in the formulation of prolonged release dosage forms. The future of novel drug delivery systems (SR) is promising in arena like chronopharmacotherapeutic delivery system, mucoadhesive system, chronopharmacokinetic approach, targeted drug delivery approach, particulate system that provide high assurance and adoptability. Sustained release oral formulations by Direct Compression (DC) method was a simple approach due to its rapid production, Easer, No degradative effects occurred during manufacturing, compliance.7 The suitability of drug candidates for sustained release system based on biopharmaceutical, pharmacokinetic and pharmacodynamic properties of it. numerous studies have been reported in the literature regarding the utilisation
{"title":"Design, development, and in vitro evaluation of sustained release tablet formulations of olmesartan medoxomil","authors":"R. Gunda, Prasada Rao Manchineni, D. Dhachinamoorthi","doi":"10.15406/mojddt.2018.02.00043","DOIUrl":"https://doi.org/10.15406/mojddt.2018.02.00043","url":null,"abstract":"Enteral route is the most comfortable, extensively used route of administration for both prompt delivery systems and new drug delivery systems. Tablets are the most famous solid formulations available in the market and are preferred by patients and physicians alike. In case of treatment of chronic disease conditions, conventional release formulations are required to be administered in frequent manner and therefore shows patient non‒adherence to prescription.1 However, ingestion of majority of drugs shows first pass effect and/or first pass hepatic metabolism presystemic elimination by gastrointestinal degradation as a result of which low systemic bioavailability and shorter duration of action and development of non‒active or toxic transformed products.2 The objective of a sustained release (SR) dosage form is to maintain CSS levels for prolonged period. Systems that are designated as modified release/timed release can also be considered as attempts at achieving prolonged drug delivery.3‒6 SR formulations offers greater reduction in dosing frequency in comparison with immediate release formulations.7 SR formulations afford advantage over prompt release formulations by optimising biopharmaceutical, pharmacokinetic and pharmacodynamic properties of drug. The utilization of macromolecules like polymers in modulating the rate of drug release has turn to an essential tool in the product development of pharmaceutical formulations. Numerous reports over many years reveals that they play key role in the release of drugs from dosage form for various drugs.8 Natural polymers preferred primarily because they were economic, high drug holding capacity, high thermal stability, non‒carcinogenicity, mucoadhesivity, biodegradable, biocompatible, broad regulatory acceptance and ease of compression. Various gums and mucilages were used for the development of sustained release formulations in such as gums (xanthan, tragacanth, guar), pectin, alginates etc. cellulose derivatives such as HPC, HPMC, CMC, SCMC have been widely used as release retardants in the formulation of prolonged release dosage forms. The future of novel drug delivery systems (SR) is promising in arena like chronopharmacotherapeutic delivery system, mucoadhesive system, chronopharmacokinetic approach, targeted drug delivery approach, particulate system that provide high assurance and adoptability. Sustained release oral formulations by Direct Compression (DC) method was a simple approach due to its rapid production, Easer, No degradative effects occurred during manufacturing, compliance.7 The suitability of drug candidates for sustained release system based on biopharmaceutical, pharmacokinetic and pharmacodynamic properties of it. numerous studies have been reported in the literature regarding the utilisation","PeriodicalId":18704,"journal":{"name":"MOJ Drug Design Development & Therapy","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76051776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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