Pub Date : 2023-01-01DOI: 10.2174/2772434418666230119101350
Sourav Sen, Nitin Kumar
Ever since the coronavirus disease 2019 (COVID-19) pandemic struck, the challenges posed to the scientific community by its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been countless, and still continue to emerge. Even though a host of repurposed and new therapeutic agents as well as vaccines have been, and are being assessed at a breakneck speed, this contagion continues to create havoc, returning back in waves, with appearance of newer viral variants which are associated with numerous challenges, which include greater transmissibility, increased virulence, immune escape, etc. In this study, we discuss the current status of various therapeutic agents which are being used, or in the various stages of preclinical/clinical trials for managing COVID-19.
{"title":"SARS-CoV-2 Pandemic-Therapeutics in Warp Speed.","authors":"Sourav Sen, Nitin Kumar","doi":"10.2174/2772434418666230119101350","DOIUrl":"https://doi.org/10.2174/2772434418666230119101350","url":null,"abstract":"<p><p>Ever since the coronavirus disease 2019 (COVID-19) pandemic struck, the challenges posed to the scientific community by its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been countless, and still continue to emerge. Even though a host of repurposed and new therapeutic agents as well as vaccines have been, and are being assessed at a breakneck speed, this contagion continues to create havoc, returning back in waves, with appearance of newer viral variants which are associated with numerous challenges, which include greater transmissibility, increased virulence, immune escape, etc. In this study, we discuss the current status of various therapeutic agents which are being used, or in the various stages of preclinical/clinical trials for managing COVID-19.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 2","pages":"110-119"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9864347","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 : 2023-01-01DOI: 10.2174/2772434418666230228121730
Alpana Kulkarni, Priya Betai
Background: Tuberculosis (TB) is still a major cause of death worldwide, despite possibly curable therapies. Neurotoxicity, optic neuritis, and severe liver damage are side effects of isoniazid, a powerful first-line anti-TB drug.
Objective: We investigated the use of PCL-PEG copolymer to sustain the release of isoniazid to reduce its adverse effects.
Methods: In the present work, PCL-PEG copolymer was synthesized and characterized. Isoniazid-loaded nanoparticles (Inp) were prepared using a PCL-PEG copolymer. Furthermore, a 23 half factorial design was employed for the optimization of drug and emulsifier concentration in Inp. Full characterization of the nanoparticles was performed in terms of drug loading, entrapment efficiency, particle size, zeta potential, and in vitro drug release. The morphology, FTIR, DSC, and PXRD evaluation of the optimized Batch Inp F13 were studied. Stability was evaluated by storing the freeze-dried Inp F13 at various temperatures.
Results: The entrapment efficiency and drug loading of nanoparticles prepared by double emulsion solvent evaporation were found to be the highest. The release study revealed that all batches of nanoparticles exhibited sustained drug release (60.26 - 88.59%) for 5 days. The cytotoxicity study conducted on Mycobacterium tuberculosis revealed a gradual release of isoniazid from Inp, reaching the maximum (on the 15th day) compared to plain isoniazid (on the 4th day). At 0.8 μg/mL concentration, the inhibitory activity of Inp F13 was maintained for 15 days, indicating sustained release of isoniazid.
Conclusion: The nanoparticles having PCL:PEG in a 95:5 ratio, with 0.5% PVA and initial drug loading of 3 mg, produced the optimum batch. Isoniazid-loaded PCL-PEG nanoparticles allowed controlled (sustained) release of isoniazid.
{"title":"Isoniazid Loaded PCL-PEG Copolymer Nanoparticles for Sustained Release Application.","authors":"Alpana Kulkarni, Priya Betai","doi":"10.2174/2772434418666230228121730","DOIUrl":"https://doi.org/10.2174/2772434418666230228121730","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is still a major cause of death worldwide, despite possibly curable therapies. Neurotoxicity, optic neuritis, and severe liver damage are side effects of isoniazid, a powerful first-line anti-TB drug.</p><p><strong>Objective: </strong>We investigated the use of PCL-PEG copolymer to sustain the release of isoniazid to reduce its adverse effects.</p><p><strong>Methods: </strong>In the present work, PCL-PEG copolymer was synthesized and characterized. Isoniazid-loaded nanoparticles (Inp) were prepared using a PCL-PEG copolymer. Furthermore, a 2<sup>3</sup> half factorial design was employed for the optimization of drug and emulsifier concentration in Inp. Full characterization of the nanoparticles was performed in terms of drug loading, entrapment efficiency, particle size, zeta potential, and in vitro drug release. The morphology, FTIR, DSC, and PXRD evaluation of the optimized Batch Inp F13 were studied. Stability was evaluated by storing the freeze-dried Inp F13 at various temperatures.</p><p><strong>Results: </strong>The entrapment efficiency and drug loading of nanoparticles prepared by double emulsion solvent evaporation were found to be the highest. The release study revealed that all batches of nanoparticles exhibited sustained drug release (60.26 - 88.59%) for 5 days. The cytotoxicity study conducted on <i>Mycobacterium tuberculosis </i>revealed a gradual release of isoniazid from Inp, reaching the maximum (on the 15<sup>th</sup> day) compared to plain isoniazid (on the 4<sup>th</sup> day). At 0.8 μg/mL concentration, the inhibitory activity of Inp F13 was maintained for 15 days, indicating sustained release of isoniazid.</p><p><strong>Conclusion: </strong>The nanoparticles having PCL:PEG in a 95:5 ratio, with 0.5% PVA and initial drug loading of 3 mg, produced the optimum batch. Isoniazid-loaded PCL-PEG nanoparticles allowed controlled (sustained) release of isoniazid.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 3","pages":"221-238"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947808","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}
Introduction: Steroids have shown its usefulness in critically ill COVID-19 patients. However, the time of starting steroid and dose tailored to severity remain a matter of inquiry due to still emerging evidences and wide-ranging concerns of benefits and harms. We did a retrospective record analysis in an apex teaching hospital ICU setting to explore optimal doses and duration of steroid therapy which can decrease mortality.
Methods: 114 adults with COVID-19-ARDS admitted to ICU between 20th March-15th August 2020 were included in chart review. We did preliminary exploratory analysis (rooted in steroid therapy matrix categorized by dose and duration) to understand the effect of several covariates on survival. This was followed by univariate and multivariate Cox proportion hazard regression analysis and model diagnostics.
Results: Exploratory analysis and visualization indicated age, optimal steroid, severity (measured in P/F) of disease and infection status as potential covariates for survival. Univariate cox regression analysis showed significant positive association of age > 60 years {2.6 (1.5-4.7)} and protective effect of optimum steroid {0.38(0.2-0.72)} on death (hazard) in critically ill patients. Multivariate cox regression analysis after adjusting effect of age showed protective effect of optimum steroid on hazard defined as death {0.46(0.23-0.87), LR = 17.04, (p = 2e-04)}. The concordance was 0.70 and model diagnostics fulfilled the assumption criteria for proportional hazard model.
Conclusion: Optimal dose steroid as per defined 'optimum' (<24 hours and doses tailored to P/F at presentation) criteria can offer protective effect from mortality which persists after adjusting for age. This protective effect was not found to be negatively influenced by the risk of infection.
{"title":"Whether Early Steroid dose is Associated with Lower Mortality in COVID-19 Critically Ill Patients-An Exploratory Chart Review.","authors":"Abhishek Goyal, Ankur Joshi, Saurabh Saigal, Dodda Brahmam, Yogesh Niwariya, Alkesh Khurana, Sagar Khadanga, Arun Mitra","doi":"10.2174/2772434417666220817121439","DOIUrl":"https://doi.org/10.2174/2772434417666220817121439","url":null,"abstract":"<p><strong>Introduction: </strong>Steroids have shown its usefulness in critically ill COVID-19 patients. However, the time of starting steroid and dose tailored to severity remain a matter of inquiry due to still emerging evidences and wide-ranging concerns of benefits and harms. We did a retrospective record analysis in an apex teaching hospital ICU setting to explore optimal doses and duration of steroid therapy which can decrease mortality.</p><p><strong>Methods: </strong>114 adults with COVID-19-ARDS admitted to ICU between 20th March-15th August 2020 were included in chart review. We did preliminary exploratory analysis (rooted in steroid therapy matrix categorized by dose and duration) to understand the effect of several covariates on survival. This was followed by univariate and multivariate Cox proportion hazard regression analysis and model diagnostics.</p><p><strong>Results: </strong>Exploratory analysis and visualization indicated age, optimal steroid, severity (measured in P/F) of disease and infection status as potential covariates for survival. Univariate cox regression analysis showed significant positive association of age > 60 years {2.6 (1.5-4.7)} and protective effect of optimum steroid {0.38(0.2-0.72)} on death (hazard) in critically ill patients. Multivariate cox regression analysis after adjusting effect of age showed protective effect of optimum steroid on hazard defined as death {0.46(0.23-0.87), LR = 17.04, (p = 2e-04)}. The concordance was 0.70 and model diagnostics fulfilled the assumption criteria for proportional hazard model.</p><p><strong>Conclusion: </strong>Optimal dose steroid as per defined 'optimum' (<24 hours and doses tailored to P/F at presentation) criteria can offer protective effect from mortality which persists after adjusting for age. This protective effect was not found to be negatively influenced by the risk of infection.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 1","pages":"42-53"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111169","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 : 2022-11-01DOI: 10.2174/277243441703221110095800
A. Tsakris
{"title":"Meet the Regional Editor","authors":"A. Tsakris","doi":"10.2174/277243441703221110095800","DOIUrl":"https://doi.org/10.2174/277243441703221110095800","url":null,"abstract":"","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77855522","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 : 2022-08-01DOI: 10.2174/277243441702221007104933
Michael R. Hamblin
{"title":"Meet the Regional Editor","authors":"Michael R. Hamblin","doi":"10.2174/277243441702221007104933","DOIUrl":"https://doi.org/10.2174/277243441702221007104933","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81935839","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 : 2022-06-10DOI: 10.2174/2772434417666220610110226
A. Mekawey, Salah A R, Mohammed Yosri
BACKGROUND Biomphalaria alexandrina snails, as transitional hosts of schistosomiasis, plays an essential part in spread of the illness. Control of these snails by the substance molluscicides antagonistically influences the oceanic climate, causing poisonous and cancer-causing consequences for non-target life forms. OBJECTIVE Looking for new naturally safe substances can be used for treatment of schistosomiasis disease with minimal side effects on environment and plants, fish wealth and did not affect on human vital functions. METHODS Fifty fungal species were used to evaluate their activity against Biomphalaria alexandrina. Study the effect of fungal extract on vital functions of Biomphalaria alexandrina and fish wealth. Purification of active substances and identification of their chemical structures. Results Cladosporium nigrellum and Penicillium aurantiogresium metabolites were effective against B. alexandrina snails, the effects of promising fungal extracts sub-lethal concentrations (IC10 & IC25) on the levels of steroid sex hormones, liver enzymes, total protein, lipids, albumin and glucose were determined. Chemical analyses of this filtrate resulted in the separation of a compound effective against snails; it was identified. Protein electrophoresis showed that fungal filtrate affects the protein pattern of snails' haemolymph. Little or no mortality of Daphnia pulex individuals was observed after their exposure to sub lethal concentrations of each treatment. CONCLUSION Certain compounds from fungal cultures could be safely used for biological control of Biomphalaria alexandrina snails.
{"title":"A study on the bio-responses of a freshwater snail (Biomphalaria alexandrina) to fungal derived compounds.","authors":"A. Mekawey, Salah A R, Mohammed Yosri","doi":"10.2174/2772434417666220610110226","DOIUrl":"https://doi.org/10.2174/2772434417666220610110226","url":null,"abstract":"BACKGROUND\u0000Biomphalaria alexandrina snails, as transitional hosts of schistosomiasis, plays an essential part in spread of the illness. Control of these snails by the substance molluscicides antagonistically influences the oceanic climate, causing poisonous and cancer-causing consequences for non-target life forms.\u0000\u0000\u0000OBJECTIVE\u0000Looking for new naturally safe substances can be used for treatment of schistosomiasis disease with minimal side effects on environment and plants, fish wealth and did not affect on human vital functions.\u0000\u0000\u0000METHODS\u0000Fifty fungal species were used to evaluate their activity against Biomphalaria alexandrina. Study the effect of fungal extract on vital functions of Biomphalaria alexandrina and fish wealth. Purification of active substances and identification of their chemical structures. Results Cladosporium nigrellum and Penicillium aurantiogresium metabolites were effective against B. alexandrina snails, the effects of promising fungal extracts sub-lethal concentrations (IC10 & IC25) on the levels of steroid sex hormones, liver enzymes, total protein, lipids, albumin and glucose were determined. Chemical analyses of this filtrate resulted in the separation of a compound effective against snails; it was identified. Protein electrophoresis showed that fungal filtrate affects the protein pattern of snails' haemolymph. Little or no mortality of Daphnia pulex individuals was observed after their exposure to sub lethal concentrations of each treatment.\u0000\u0000\u0000CONCLUSION\u0000Certain compounds from fungal cultures could be safely used for biological control of Biomphalaria alexandrina snails.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82306242","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 : 2022-06-09DOI: 10.2174/2772434417666220609105755
R. Das, D. Mehta, Sumeet Gupta, Meenakshi Dhanawat
BACKGROUND Chemical modification of Oxadiazole may lead to a potent therapeutic agent. A series of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives (5a-g) have been synthesised utilising pyrazinoic acid as a precursor. The new oxadiazole compounds were docked against potential targets and evaluated for antibacterial and antitubercular activity. METHODS The 5-pyrazyl-2-substituted sulfanyl-1,3,4-oxadiazole derivatives (5a-g) were synthesized from the crucial intermediate 2-sulfanyl-5-pyrazyl-1,3,4-oxadiazole (4), which was prepared by treating the 2-pyrazyl hydrazide with CS2 and pyridine. IR, 1HNMR, 13C, MS and elemental analyses were used to confirm the chemical structures. RESULTS Antimicrobial activity was determined for each synthesized compound. Additionally, compounds were evaluated for antitubercular activity against the Mycobacterium Tuberculosis H37Rv strain. Compounds 5c, 5g, and 5a had a favourable antibacterial profile, while 5c and 5g (MIC = 25 g/ml) demonstrated potential antitubercular activity when compared to the other produced compounds. Molecular docking experiments using V-Life Science MDS 4.6 supplemented the biological data. CONCLUSION Each compound has been tested for antibacterial and antitubercular action against a variety of microorganism strains and exhibits considerable activity. Additionally, molecular docking analysis confirmed the experimental results by describing improved interaction patterns.
{"title":"Design, Synthesis, Anti-microbial and Molecular Docking Studies of Novel 5-Pyrazyl-2-Sulfanyl-1, 3, 4-Oxadiazole Derivatives.","authors":"R. Das, D. Mehta, Sumeet Gupta, Meenakshi Dhanawat","doi":"10.2174/2772434417666220609105755","DOIUrl":"https://doi.org/10.2174/2772434417666220609105755","url":null,"abstract":"BACKGROUND\u0000Chemical modification of Oxadiazole may lead to a potent therapeutic agent. A series of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives (5a-g) have been synthesised utilising pyrazinoic acid as a precursor. The new oxadiazole compounds were docked against potential targets and evaluated for antibacterial and antitubercular activity.\u0000\u0000\u0000METHODS\u0000The 5-pyrazyl-2-substituted sulfanyl-1,3,4-oxadiazole derivatives (5a-g) were synthesized from the crucial intermediate 2-sulfanyl-5-pyrazyl-1,3,4-oxadiazole (4), which was prepared by treating the 2-pyrazyl hydrazide with CS2 and pyridine. IR, 1HNMR, 13C, MS and elemental analyses were used to confirm the chemical structures.\u0000\u0000\u0000RESULTS\u0000Antimicrobial activity was determined for each synthesized compound. Additionally, compounds were evaluated for antitubercular activity against the Mycobacterium Tuberculosis H37Rv strain. Compounds 5c, 5g, and 5a had a favourable antibacterial profile, while 5c and 5g (MIC = 25 g/ml) demonstrated potential antitubercular activity when compared to the other produced compounds. Molecular docking experiments using V-Life Science MDS 4.6 supplemented the biological data.\u0000\u0000\u0000CONCLUSION\u0000Each compound has been tested for antibacterial and antitubercular action against a variety of microorganism strains and exhibits considerable activity. Additionally, molecular docking analysis confirmed the experimental results by describing improved interaction patterns.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74371927","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 : 2022-06-06DOI: 10.2174/2772434417666220606105822
Chime Salome A, A. A., Onunkwo Godswill C
BACKGROUND Artemisinin based combination therapies (ACTs) typified by dihydroartemisinin-piperaquine phosphate is one of the first line drugs used in the treatment of Plasmodium falciparum malaria. However, the emergence of drug resistance to ACTs show the necessity to develop novel sustained release treatment in order to ensure maximum bioavailability. OBJECTIVES To formulate dihydroartemisinin (DHA)-piperaquine phosphate (PQ) sustained release tablets based on solidified reverse micellar solutions (SRMS). METHODS The SRMS was prepared by fusion using varying ratios of Phospholipon® 90H and Softisan® 154 and characterised. The tablets were prepared by using an in-house made and validated mould. The formulations were tested for uniformity of weight, hardness, friability, softening time, erosion time and in vitro-in vivo dissolution rate. Anti malarial properties were studied by modified Peter's 4-days suppressive test in mice. One-way analysis of variance (ANOVA) was used in analysis of results. RESULTS Smooth caplets, with average weight of 1300 ± 0.06 to 1312 ± 0.11 mg, drug content of 61 mg for DHA and t 450 mg for PQ. Tablets hardness ranged from 7.1 to 9.0 Kgf and softening time of 29.50 ± 1.90 min. Erosion time of 62.00 ± 2.58 to 152.00 ± 1.89 min were obtained for tablets formulated with Poloxamer 188 (Batches R2, S2 and T2) which significantly reduced the softening and erosion time (p < 0.05). In vitro release showed that optimized formulation had maximum release at 12 h. Formulations exhibited significantly higher parasitaemia clearance and in vivo absorption compared to marketed formulations at day 7 (p < 0.05). CONCLUSION DHA-PQ tablets based on SRMS is much easier and relatively cheaper to produce than compressed tablets. They also showed exceptionally better treatment of malaria owing to their sustained release properties and improved bioavailability and is recommended to Pharmaceutical companies for further studies.
{"title":"Assessment of the anti-malarial properties of dihydroartemisinin-piperaquine phosphate solid lipid-based tablets.","authors":"Chime Salome A, A. A., Onunkwo Godswill C","doi":"10.2174/2772434417666220606105822","DOIUrl":"https://doi.org/10.2174/2772434417666220606105822","url":null,"abstract":"BACKGROUND\u0000Artemisinin based combination therapies (ACTs) typified by dihydroartemisinin-piperaquine phosphate is one of the first line drugs used in the treatment of Plasmodium falciparum malaria. However, the emergence of drug resistance to ACTs show the necessity to develop novel sustained release treatment in order to ensure maximum bioavailability.\u0000\u0000\u0000OBJECTIVES\u0000To formulate dihydroartemisinin (DHA)-piperaquine phosphate (PQ) sustained release tablets based on solidified reverse micellar solutions (SRMS).\u0000\u0000\u0000METHODS\u0000The SRMS was prepared by fusion using varying ratios of Phospholipon® 90H and Softisan® 154 and characterised. The tablets were prepared by using an in-house made and validated mould. The formulations were tested for uniformity of weight, hardness, friability, softening time, erosion time and in vitro-in vivo dissolution rate. Anti malarial properties were studied by modified Peter's 4-days suppressive test in mice. One-way analysis of variance (ANOVA) was used in analysis of results.\u0000\u0000\u0000RESULTS\u0000Smooth caplets, with average weight of 1300 ± 0.06 to 1312 ± 0.11 mg, drug content of 61 mg for DHA and t 450 mg for PQ. Tablets hardness ranged from 7.1 to 9.0 Kgf and softening time of 29.50 ± 1.90 min. Erosion time of 62.00 ± 2.58 to 152.00 ± 1.89 min were obtained for tablets formulated with Poloxamer 188 (Batches R2, S2 and T2) which significantly reduced the softening and erosion time (p < 0.05). In vitro release showed that optimized formulation had maximum release at 12 h. Formulations exhibited significantly higher parasitaemia clearance and in vivo absorption compared to marketed formulations at day 7 (p < 0.05).\u0000\u0000\u0000CONCLUSION\u0000DHA-PQ tablets based on SRMS is much easier and relatively cheaper to produce than compressed tablets. They also showed exceptionally better treatment of malaria owing to their sustained release properties and improved bioavailability and is recommended to Pharmaceutical companies for further studies.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88173535","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 : 2022-05-31DOI: 10.2174/1570193X19666220531154544
D. Bhosale, Suraj N. Mali, B. Thorat, Swati S Wavhal, D. Bhagat, R. M. Borade
BACKGROUND Mycobacterium tuberculosis (Mtb) is the organism that causes tuberculosis to develop (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones-hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication. OBJECTIVES We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature. MATERIALS AND METHODS All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial analysis, H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors. RESULTS Among all tested molecules, 3i (MIC: 50 μg/mL) and 3b (MIC: 50 μg/mL) were found to best ligands for further development of new anti-TB drug. We noticed that our proposed molecules were having higher docking scores that corresponding standard anti-TB agents such as Ciprofloxacin and Isoniazid. Synthesized compounds were found to have Drug-Likeness properties when tested with Lipinski's filter for drug-likeness. CONCLUSION From our current study, we wish to propose N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for developments into active lead molecules.
{"title":"Synthesis, Molecular docking and In-Vitro Antimycobacterial Studies on N'-arylidene-4-nitrobenzohydrazides.","authors":"D. Bhosale, Suraj N. Mali, B. Thorat, Swati S Wavhal, D. Bhagat, R. M. Borade","doi":"10.2174/1570193X19666220531154544","DOIUrl":"https://doi.org/10.2174/1570193X19666220531154544","url":null,"abstract":"BACKGROUND\u0000Mycobacterium tuberculosis (Mtb) is the organism that causes tuberculosis to develop (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones-hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication.\u0000\u0000\u0000OBJECTIVES\u0000We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature.\u0000\u0000\u0000MATERIALS AND METHODS\u0000All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial analysis, H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors.\u0000\u0000\u0000RESULTS\u0000Among all tested molecules, 3i (MIC: 50 μg/mL) and 3b (MIC: 50 μg/mL) were found to best ligands for further development of new anti-TB drug. We noticed that our proposed molecules were having higher docking scores that corresponding standard anti-TB agents such as Ciprofloxacin and Isoniazid. Synthesized compounds were found to have Drug-Likeness properties when tested with Lipinski's filter for drug-likeness.\u0000\u0000\u0000CONCLUSION\u0000From our current study, we wish to propose N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for developments into active lead molecules.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82837193","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 : 2022-05-18DOI: 10.2174/1574891X16666220518142347
A. M. Santos, Mariana Mendonça Santos, José Adão Carvalho Nascimento Júnior, João Rafael Lisboa Rêgo Brito, Tatianny de Araújo Andrade, L. Frank, M. Serafini
BACKGROUND The worldwide pandemic fought by COVID-19 could emerge another type of pandemic, the increase in bacterial resistance against antibiotics. Emergency treatment based on antibioticsis a major influence in increasing this resistance. Bacteria, such as Klebsiella pneumoniae, are most affected by the indiscriminate use of antibiotics since they are resistant to most antibiotics currently available on the market. OBJECTIVE This review aimed to evaluate patents of new drugs and formulations, for the treatment of infections caused by Klebsiella pneumoniae. METHODS The present patent review was carried out through a specialized search database Espacenet. The selection was based on the criteria of patents published from 2010 to May 2021, in any language, and containing the keywords in title or abstract. Also, a research was performed on the PubMed database, using the inclusion criteria. RESULTS Twenty-two patents were selected for the analysis according to the aim of the study. The advance of new patents has been mostly seen in World Intellectual Property Organization, China, and United States. The results showed that the main approach was the drug association, followed by drug carriers, new isolated products, and vaccines. CONCLUSION It has been observed that few studies use new drug alternatives for the treatment, probably due to the higher cost of the development and lack of investments. The effectiveness and safety of these therapies depend on the acceptance, the correct prescription, and rational use of medicines. Therefore, this review can further develop new treatments as alternatives against Klebsiella pneumoniae and pneumonia caused by it.
{"title":"Mapping of new pharmacological alternatives in the face of the emergence of antibiotic resistance in COVID-19 patents treated for opportunistic respiratory bacterial pathogens.","authors":"A. M. Santos, Mariana Mendonça Santos, José Adão Carvalho Nascimento Júnior, João Rafael Lisboa Rêgo Brito, Tatianny de Araújo Andrade, L. Frank, M. Serafini","doi":"10.2174/1574891X16666220518142347","DOIUrl":"https://doi.org/10.2174/1574891X16666220518142347","url":null,"abstract":"BACKGROUND\u0000The worldwide pandemic fought by COVID-19 could emerge another type of pandemic, the increase in bacterial resistance against antibiotics. Emergency treatment based on antibioticsis a major influence in increasing this resistance. Bacteria, such as Klebsiella pneumoniae, are most affected by the indiscriminate use of antibiotics since they are resistant to most antibiotics currently available on the market.\u0000\u0000\u0000OBJECTIVE\u0000This review aimed to evaluate patents of new drugs and formulations, for the treatment of infections caused by Klebsiella pneumoniae.\u0000\u0000\u0000METHODS\u0000The present patent review was carried out through a specialized search database Espacenet. The selection was based on the criteria of patents published from 2010 to May 2021, in any language, and containing the keywords in title or abstract. Also, a research was performed on the PubMed database, using the inclusion criteria.\u0000\u0000\u0000RESULTS\u0000Twenty-two patents were selected for the analysis according to the aim of the study. The advance of new patents has been mostly seen in World Intellectual Property Organization, China, and United States. The results showed that the main approach was the drug association, followed by drug carriers, new isolated products, and vaccines.\u0000\u0000\u0000CONCLUSION\u0000It has been observed that few studies use new drug alternatives for the treatment, probably due to the higher cost of the development and lack of investments. The effectiveness and safety of these therapies depend on the acceptance, the correct prescription, and rational use of medicines. Therefore, this review can further develop new treatments as alternatives against Klebsiella pneumoniae and pneumonia caused by it.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79598936","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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