Pub Date : 2023-11-30DOI: 10.25004/ijpsdr.2023.150610
Rashmi Bagri, N. Ravouru
Ibrutinib (IB), irreversibly inhibits Bruton’s tyrosine kinase which plays a crucial role in the tumor microenvironment and quercetin (QC) has shown apoptosis induction, angiogenesis inhibition, and anti-proliferative action against several human carcinoma cells. The self-nano-emulsifying drug delivery system (SNEDDS) is suitable for loading insolubilized oil-based compounds such as ibrutinib and quercetin. In the current study IB with QC was formulated into SNEDDS and cytotoxicity was determined by using human malignant melanoma (A-375) and human lung adenocarcinoma (A549) cell lines. The optimized loaded formula consisted of castor oil, Kolliphor® RH 40, and PEG-600. The optimized formulation was evaluated for physical parameters and the results were satisfactory. For cytotoxicity studies MTT assay was conducted for these combinations, IC50 values were calculated for the tested compound. In A-549 adenocarcinoma cell line, the calculated IC50 values (μM) for the test compounds T1 (pure IB ± QC) and T2 (IB ± QC SNEDDS) were 70.34 ± 0.8 and 85.46 ± 0.93 μM at 24 hours study, respectively. In A-375 cancer cell line, IC50 values for the compounds T1 and T2 were 59.52 ± 0.87 and 88.43 ± 1.03 μM for 24 hours study, respectively. It was observed that the IC50 of IB-QC loaded SNEDDS was higher than pure drug combination and these enter the cells by active transport and induce cytotoxicity to the cells. The overall results from the studies suggest that IB-QC-loaded SNEDD provided synergistic effects, which could play a significant role in the percentage of cell death.
{"title":"Studies on Fixed Dose Combination of Ibrutinib and Quercetin Self-Nanoemulsifying Drug Delivery Systems in Human Cancer Cell Lines","authors":"Rashmi Bagri, N. Ravouru","doi":"10.25004/ijpsdr.2023.150610","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150610","url":null,"abstract":"Ibrutinib (IB), irreversibly inhibits Bruton’s tyrosine kinase which plays a crucial role in the tumor microenvironment and quercetin (QC) has shown apoptosis induction, angiogenesis inhibition, and anti-proliferative action against several human carcinoma cells. The self-nano-emulsifying drug delivery system (SNEDDS) is suitable for loading insolubilized oil-based compounds such as ibrutinib and quercetin. In the current study IB with QC was formulated into SNEDDS and cytotoxicity was determined by using human malignant melanoma (A-375) and human lung adenocarcinoma (A549) cell lines. The optimized loaded formula consisted of castor oil, Kolliphor® RH 40, and PEG-600. The optimized formulation was evaluated for physical parameters and the results were satisfactory. For cytotoxicity studies MTT assay was conducted for these combinations, IC50 values were calculated for the tested compound. In A-549 adenocarcinoma cell line, the calculated IC50 values (μM) for the test compounds T1 (pure IB ± QC) and T2 (IB ± QC SNEDDS) were 70.34 ± 0.8 and 85.46 ± 0.93 μM at 24 hours study, respectively. In A-375 cancer cell line, IC50 values for the compounds T1 and T2 were 59.52 ± 0.87 and 88.43 ± 1.03 μM for 24 hours study, respectively. It was observed that the IC50 of IB-QC loaded SNEDDS was higher than pure drug combination and these enter the cells by active transport and induce cytotoxicity to the cells. The overall results from the studies suggest that IB-QC-loaded SNEDD provided synergistic effects, which could play a significant role in the percentage of cell death.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139208910","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150602
Nandini Bansod, Mani P Goutam
information regarding drug abuse and pharmaceutical use. In recent years, drug analysis in human nail clippings has proven its significant value in forensic toxicological applications, identification of in utero drug exposure, monitoring of drug treatment programmes, and therapeutic drug monitoring. Nails have various advantages over conventional matrices (blood and urine), which include a longer detection window (months to years), non-invasive sample collection, and easy storage and transportation. These aspects make nails a very significant matrix for forensic toxicology and therapeutic drug monitoring. Because of the low concentrations of drugs of abuse and pharmaceuticals present in nails and the complexity of the keratinized matrix, analytical techniques need to be more sensitive, and sample preparation is crucial. The aim of the present study is to develop a simple, high-performance liquid chromatography-mass spectroscopy (LC-MS) method for the identification and quantitation of 3,4-methylenedioxyamphetamine (MDA) in fingernail and toenail clippings. Finger and toenail clippings were collected from six users undergoing treatment at a rehab center in Ujjain, M.P., India. Nail clippings were initially decontaminated, then hydrolyzed in 1 M NaOH at 370°C, extracted with ethyl acetate, diluted with methanol, and then subjected to LC-MS analysis. The calibration curve was constructed over the 0.5 to 30 ng/mL concentration range using the MDA reference standard. The limit of detection was calculated at 1.10 ng/mL and the limit of quantification was recorded at 3.67 ng/mL in standard solutions, whereas the respective values in spiked nail clippings were 1.21 and 4.6 ng/mg. The developed method has obtained significant results in original nail clippings with mean concentration ranges of 0.12 ng/mg in fingernails and 0.08 ng/mg in toenails in six abuser samples. The new method developed has been found to be capable of detecting the 3,4-methylendioxyamphetamine MDA drug in nail clippings even after 90 days of drug intake.
{"title":"Detection of 3-4 Methylenedioxyamphetamine from Drug Abuser’s Fingers and Toenails using Liquid Chromatography with Mass Spectroscopy","authors":"Nandini Bansod, Mani P Goutam","doi":"10.25004/ijpsdr.2023.150602","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150602","url":null,"abstract":"information regarding drug abuse and pharmaceutical use. In recent years, drug analysis in human nail clippings has proven its significant value in forensic toxicological applications, identification of in utero drug exposure, monitoring of drug treatment programmes, and therapeutic drug monitoring. Nails have various advantages over conventional matrices (blood and urine), which include a longer detection window (months to years), non-invasive sample collection, and easy storage and transportation. These aspects make nails a very significant matrix for forensic toxicology and therapeutic drug monitoring. Because of the low concentrations of drugs of abuse and pharmaceuticals present in nails and the complexity of the keratinized matrix, analytical techniques need to be more sensitive, and sample preparation is crucial. The aim of the present study is to develop a simple, high-performance liquid chromatography-mass spectroscopy (LC-MS) method for the identification and quantitation of 3,4-methylenedioxyamphetamine (MDA) in fingernail and toenail clippings. Finger and toenail clippings were collected from six users undergoing treatment at a rehab center in Ujjain, M.P., India. Nail clippings were initially decontaminated, then hydrolyzed in 1 M NaOH at 370°C, extracted with ethyl acetate, diluted with methanol, and then subjected to LC-MS analysis. The calibration curve was constructed over the 0.5 to 30 ng/mL concentration range using the MDA reference standard. The limit of detection was calculated at 1.10 ng/mL and the limit of quantification was recorded at 3.67 ng/mL in standard solutions, whereas the respective values in spiked nail clippings were 1.21 and 4.6 ng/mg. The developed method has obtained significant results in original nail clippings with mean concentration ranges of 0.12 ng/mg in fingernails and 0.08 ng/mg in toenails in six abuser samples. The new method developed has been found to be capable of detecting the 3,4-methylendioxyamphetamine MDA drug in nail clippings even after 90 days of drug intake.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139198992","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150601
Pankaj Sharma, Chandra S Sharma
A series of novel isoxazole-incorporated benzimidazole derivatives was synthesized and investigated for antimicrobial activity. The structures of all synthesized compounds were confirmed by means of elemental analysis, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and liquid chromatography-mass spectrometry (LC-MS). All compounds were evaluated for antimicrobial activity cup plate method against Staphylococcus aureus, Bacillus anthracis, Pseudomonas aeruginosa, Escherchia coli, Candida albicans and Aspegillus niger. The 4d, 4f and 4j compounds showed significant activity against gram-positive and gram-negative bacteria. On the basis of the interaction energy criterion, compound 4f showed the best docking interactions equal to 7.0 kcal/mol.
{"title":"Synthesis, Antimicrobial Activity and Molecular Docking Study of Some Novel Isoxazole Incorporated Benzimidazole Derivatives","authors":"Pankaj Sharma, Chandra S Sharma","doi":"10.25004/ijpsdr.2023.150601","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150601","url":null,"abstract":"A series of novel isoxazole-incorporated benzimidazole derivatives was synthesized and investigated for antimicrobial activity. The structures of all synthesized compounds were confirmed by means of elemental analysis, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and liquid chromatography-mass spectrometry (LC-MS). All compounds were evaluated for antimicrobial activity cup plate method against Staphylococcus aureus, Bacillus anthracis, Pseudomonas aeruginosa, Escherchia coli, Candida albicans and Aspegillus niger. The 4d, 4f and 4j compounds showed significant activity against gram-positive and gram-negative bacteria. On the basis of the interaction energy criterion, compound 4f showed the best docking interactions equal to 7.0 kcal/mol.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"166 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139202619","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150603
N. A. Belho, Rukutalu Veswuh, Peter Solo
Entada rheedei Spreng., is a liana or a climber belonging to the family Fabaceae and is widely distributed in tropical and subtropical areas. The seeds of E. rheedei Spreng. has been found to contain important phytoconstituents such as phenolics, thioamides and saponins. In this study, we investigated the antifungal properties of E. rheedei Spreng. and imply in-silico methods to study its bioactive phytoconstituents. The aqueous extract of the seeds exhibited significant antifungal inhibitions against Aspergillus flavus and A. fumigatus. GC-MS analysis reveals the presence of 13 bioactive compounds that could be potent fungal inhibitors. Subsequently, in-silico Molecular docking analysis recognised benzoic acid, 2, 4-bis (trimethylsilyloxy)- trimethylsilyl ester as the active antifungal constituent of the aqueous extract with a docking score of -8.0570 and -9.4564 kcal/mol against A. flavus and A. fumigatus respectively. The in-silico studies were further backed by 100 ns molecular dDynamics simulation studies. This study can thus lead to the production of potent plant-based antifungal drugs.
{"title":"GC-MS Analysis and In-silico Docking Study of Active Antifungal Components of Entada rheedei Spreng. (Seeds)","authors":"N. A. Belho, Rukutalu Veswuh, Peter Solo","doi":"10.25004/ijpsdr.2023.150603","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150603","url":null,"abstract":"Entada rheedei Spreng., is a liana or a climber belonging to the family Fabaceae and is widely distributed in tropical and subtropical areas. The seeds of E. rheedei Spreng. has been found to contain important phytoconstituents such as phenolics, thioamides and saponins. In this study, we investigated the antifungal properties of E. rheedei Spreng. and imply in-silico methods to study its bioactive phytoconstituents. The aqueous extract of the seeds exhibited significant antifungal inhibitions against Aspergillus flavus and A. fumigatus. GC-MS analysis reveals the presence of 13 bioactive compounds that could be potent fungal inhibitors. Subsequently, in-silico Molecular docking analysis recognised benzoic acid, 2, 4-bis (trimethylsilyloxy)- trimethylsilyl ester as the active antifungal constituent of the aqueous extract with a docking score of -8.0570 and -9.4564 kcal/mol against A. flavus and A. fumigatus respectively. The in-silico studies were further backed by 100 ns molecular dDynamics simulation studies. This study can thus lead to the production of potent plant-based antifungal drugs.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139199450","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150613
Ummehani A Razvi, Laxmikant H Kamble
Depression is one of the major mental health problems at prevalence nowdays. It can be characterized by poor concentration, low self-esteem, losing interest in family or social life, feeling tired or fatigued, suicidal thoughts and similar symptoms. There are treatments like psychotherapies, anti-depressants and electroconvulsive therapies available, but there is need to identify more effective treatments with lesser side effects. Marine organisms like algae, sponges or corals have been investigated to explore their potential as anti-depressants. This article aims to explore the potential of some compounds from marine algae by molecular docking and assessment of pharmacokinetics. Human norepinephrine transporter (hNET) was used as target for this study as this transporter is responsible to reuptake norepinephrine and disturbs the chemical balance of the brain, which can be a cause for depression. These compounds’ Binding affinity was compared with the binding affinity of prescribed levomilnacipran. From 14 selected compounds, 13 showed higher binding affinity towards hNET. Among all compounds, saringosterone has the highest binding score. Pharmacokinetics properties were constructive for most compounds. Compounds showed weaker druglikeness and drugs score but can be optimized to enhance it. Compounds identified as inhibitors of NET can be developed as drug molecules in the future or algal sources for it can be taken as a food supplement.
抑郁症是当今流行的主要精神健康问题之一。它表现为注意力不集中、自卑、对家庭或社会生活失去兴趣、感到疲倦或乏力、有自杀念头等类似症状。目前有心理疗法、抗抑郁剂和电休克疗法等治疗方法，但需要找到副作用较小的更有效的治疗方法。人们对藻类、海绵或珊瑚等海洋生物进行了研究，以探索它们作为抗抑郁剂的潜力。本文旨在通过分子对接和药代动力学评估，探索海洋藻类中一些化合物的潜力。本研究以人类去甲肾上腺素转运体（hNET）为靶标，因为该转运体负责去甲肾上腺素的再摄取，会扰乱大脑的化学平衡，从而导致抑郁症。研究人员将这些化合物的结合亲和力与处方药左旋米那西普兰的结合亲和力进行了比较。在 14 种被选中的化合物中，13 种对 hNET 具有较高的结合亲和力。在所有化合物中，沙林睾酮的结合得分最高。大多数化合物的药代动力学特性具有建设性。化合物的药物亲和性和药物得分较弱，但可以通过优化来提高药物亲和性和药物得分。被鉴定为 NET 抑制剂的化合物可在未来开发为药物分子，或将其藻类来源作为食品补充剂。
{"title":"Molecular Docking Studies to Identify Inhibitors of Norepinephrine Reuptake from Marine Algae","authors":"Ummehani A Razvi, Laxmikant H Kamble","doi":"10.25004/ijpsdr.2023.150613","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150613","url":null,"abstract":"Depression is one of the major mental health problems at prevalence nowdays. It can be characterized by poor concentration, low self-esteem, losing interest in family or social life, feeling tired or fatigued, suicidal thoughts and similar symptoms. There are treatments like psychotherapies, anti-depressants and electroconvulsive therapies available, but there is need to identify more effective treatments with lesser side effects. Marine organisms like algae, sponges or corals have been investigated to explore their potential as anti-depressants. This article aims to explore the potential of some compounds from marine algae by molecular docking and assessment of pharmacokinetics. Human norepinephrine transporter (hNET) was used as target for this study as this transporter is responsible to reuptake norepinephrine and disturbs the chemical balance of the brain, which can be a cause for depression. These compounds’ Binding affinity was compared with the binding affinity of prescribed levomilnacipran. From 14 selected compounds, 13 showed higher binding affinity towards hNET. Among all compounds, saringosterone has the highest binding score. Pharmacokinetics properties were constructive for most compounds. Compounds showed weaker druglikeness and drugs score but can be optimized to enhance it. Compounds identified as inhibitors of NET can be developed as drug molecules in the future or algal sources for it can be taken as a food supplement.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139205634","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150612
Smita J Pawar, Dhanashri Zope, Amol P Kale
In-silico molecular docking studies and QSAR study of benzoxazole derivatives synthesized by Kakkar et al. was done. Comparative studies of docking of 5-flurouracil and 20 compounds revealed considerable interactions, indicating the affinity of newly synthesized compounds for thymidylate synthase. The statistically significant 2D-QSAR models were developed using a molecular design suite (VLifeMDS 4.6). The study was performed with 20 compounds (data set) using sphere exclusion (SE) algorithm, random selection and manual selection methods used for the division of the data set into training and test set. Multiple linear regression [MLR] methodology with stepwise (SW) forward-backward variable selection method was used for building the QSAR models. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by k-Nearest Neighbor Molecular Field Analysis (kNN-MFA), investigating the substitutional requirements for the favorable anticancer activity against HCT 116 cell line and providing useful information in the characterization and differentiation of their binding sites. The results may be useful for further designing benzoxazole derivatives as anticancer agents prior to synthesis.
{"title":"In-silico Studies of Heterocyclic Benzoxazole Derivatives as an Anticancer Agent: Molecular Docking, 2D and 3D QSAR","authors":"Smita J Pawar, Dhanashri Zope, Amol P Kale","doi":"10.25004/ijpsdr.2023.150612","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150612","url":null,"abstract":"In-silico molecular docking studies and QSAR study of benzoxazole derivatives synthesized by Kakkar et al. was done. Comparative studies of docking of 5-flurouracil and 20 compounds revealed considerable interactions, indicating the affinity of newly synthesized compounds for thymidylate synthase. The statistically significant 2D-QSAR models were developed using a molecular design suite (VLifeMDS 4.6). The study was performed with 20 compounds (data set) using sphere exclusion (SE) algorithm, random selection and manual selection methods used for the division of the data set into training and test set. Multiple linear regression [MLR] methodology with stepwise (SW) forward-backward variable selection method was used for building the QSAR models. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by k-Nearest Neighbor Molecular Field Analysis (kNN-MFA), investigating the substitutional requirements for the favorable anticancer activity against HCT 116 cell line and providing useful information in the characterization and differentiation of their binding sites. The results may be useful for further designing benzoxazole derivatives as anticancer agents prior to synthesis.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139200925","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150609
P. Piste
The rapid synthesis of 3-[4-(1,3-benzoxazol-2-yl)phenyl]-2-aryl-1,3-thiazolidin-4-one 4(a-h) was achieved through microwave-assisted methods. This involved the reaction of Schiff bases derived from 2-(4-amino phenyl) benzoxazole 3(a-h) with ethanol, SHCH2COOH (thioglycolic acid) (1 mol, 0.92 mL), and ZnCl2 (5 mol%) under microwave irradiation (400W, 146°C) for 3 to 4 minutes, resulting in excellent yields. Compound precursors 3(a-h) were prepared from aromatic aldehydes and 2-(4-amino phenyl) benzoxazole in ethanol, followed by microwave irradiation for 1 to 2 minutes, with reaction progress monitored via TLC. The expeditious reaction time is a notable advantage of this protocol. Comprehensive structural elucidation of the synthesized compounds involved elemental analysis, IR, NMR, 13C-NMR, and mass spectroscopy. These newly synthesized compounds, 4(a-h), were subjected to in-vitro antimicrobial screening against Staphylococcus aureus, Escherichia coli, and antifungal screening against Aspergillus niger. The zone of inhibition in millimeters was measured using the cup plate method. Several compounds within the series exhibited substantial activity when compared to the standard drugs streptomycin and fluconazole.
{"title":"Expeditious Microwave-assisted Synthesis of 1,3-Benzoxazoles Incorporating Substituted Thiazolidinone Moieties","authors":"P. Piste","doi":"10.25004/ijpsdr.2023.150609","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150609","url":null,"abstract":"The rapid synthesis of 3-[4-(1,3-benzoxazol-2-yl)phenyl]-2-aryl-1,3-thiazolidin-4-one 4(a-h) was achieved through microwave-assisted methods. This involved the reaction of Schiff bases derived from 2-(4-amino phenyl) benzoxazole 3(a-h) with ethanol, SHCH2COOH (thioglycolic acid) (1 mol, 0.92 mL), and ZnCl2 (5 mol%) under microwave irradiation (400W, 146°C) for 3 to 4 minutes, resulting in excellent yields. Compound precursors 3(a-h) were prepared from aromatic aldehydes and 2-(4-amino phenyl) benzoxazole in ethanol, followed by microwave irradiation for 1 to 2 minutes, with reaction progress monitored via TLC. The expeditious reaction time is a notable advantage of this protocol. Comprehensive structural elucidation of the synthesized compounds involved elemental analysis, IR, NMR, 13C-NMR, and mass spectroscopy. These newly synthesized compounds, 4(a-h), were subjected to in-vitro antimicrobial screening against Staphylococcus aureus, Escherichia coli, and antifungal screening against Aspergillus niger. The zone of inhibition in millimeters was measured using the cup plate method. Several compounds within the series exhibited substantial activity when compared to the standard drugs streptomycin and fluconazole.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"160 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139198744","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150604
Rajendra Patel, Komal Parmar
Enzalutamide is an anticancer molecule used for prostate cancer. The goal of the study was to develop a nanosuspension of enzalutamide in order to improve its solubility and dissolution properties. High-speed homogenization method was employed to formulate the nanosuspension. Preliminary studies suggested the amount of stabilizer, homogenization time and homogenization speed as critical variables to be taken for the optimization process. Box-Behnken design was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in-vitro drug release at 10 minutes (D10) studies. Regression analysis suggested the influence of independent variables on the responses. The optimized batch obtained from the overlay plot exhibited 198.36 nm of particle size, (-33.27 mV of zeta potential and 80.47% of D10 values). The characterization studies i.e., DSC, and XRD illustrated retention in crystallinity of the drug. The drug and formulation were found to be stable over a 6-month period in accelerated stability testing. Using high speed homogenization method, the particle size of the formulation was reduced to nano-size, which was further responsible for the improvement in dissolution and bioavailability of the drug.
{"title":"Development and Optimization of Enzalutamide Nanosuspension by Design of Experiments for Dissolution Enhancement","authors":"Rajendra Patel, Komal Parmar","doi":"10.25004/ijpsdr.2023.150604","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150604","url":null,"abstract":"Enzalutamide is an anticancer molecule used for prostate cancer. The goal of the study was to develop a nanosuspension of enzalutamide in order to improve its solubility and dissolution properties. High-speed homogenization method was employed to formulate the nanosuspension. Preliminary studies suggested the amount of stabilizer, homogenization time and homogenization speed as critical variables to be taken for the optimization process. Box-Behnken design was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in-vitro drug release at 10 minutes (D10) studies. Regression analysis suggested the influence of independent variables on the responses. The optimized batch obtained from the overlay plot exhibited 198.36 nm of particle size, (-33.27 mV of zeta potential and 80.47% of D10 values). The characterization studies i.e., DSC, and XRD illustrated retention in crystallinity of the drug. The drug and formulation were found to be stable over a 6-month period in accelerated stability testing. Using high speed homogenization method, the particle size of the formulation was reduced to nano-size, which was further responsible for the improvement in dissolution and bioavailability of the drug.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"1 8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139198511","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150606
K. Raut, S. Kothawade, V.V Pande, V.S Wagh, S. Bole, R. B. Sumbe
A recent study reveals that Isatinylthiosemicarbazone analogues inhibit mycobacterial growth by inhibiting the isocitrate lyase (ICL). Hence two-dimensional (2D), three-dimensional (3D), and group QSAR (GQSAR) studies were performed to reduce the amount of pharmacophore needed to make effective ICL inhibitors. New chemical entities (NCEs) were created based on the findings of all QSAR studies. It was discovered that QSAR models produced noticeably positive statistical findings. i.e. (r2 > 0.7), cross-validation (q2 > 0.6), and external validation (pred_r2 > 0.6), indicating high predictability of all models. Utilizing molecular docking studies, the binding affinities of designed NCEs were investigated for the ICL enzyme (PDB code: 1F8M). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of designed NCEs were expected to have a pharmacokinetic profile similar to their drug. Overall, it is important to state that the methodology used for pharmacophore optimization using 2D, 3D, G-QSAR, and molecular docking ADMET research works was discovered to be extremely accurate.
{"title":"In-silico Design of Potent Anti-tubercular Agents containing Isatinylthiosemicarbazone Pharmacophore","authors":"K. Raut, S. Kothawade, V.V Pande, V.S Wagh, S. Bole, R. B. Sumbe","doi":"10.25004/ijpsdr.2023.150606","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150606","url":null,"abstract":"A recent study reveals that Isatinylthiosemicarbazone analogues inhibit mycobacterial growth by inhibiting the isocitrate lyase (ICL). Hence two-dimensional (2D), three-dimensional (3D), and group QSAR (GQSAR) studies were performed to reduce the amount of pharmacophore needed to make effective ICL inhibitors. New chemical entities (NCEs) were created based on the findings of all QSAR studies. It was discovered that QSAR models produced noticeably positive statistical findings. i.e. (r2 > 0.7), cross-validation (q2 > 0.6), and external validation (pred_r2 > 0.6), indicating high predictability of all models. Utilizing molecular docking studies, the binding affinities of designed NCEs were investigated for the ICL enzyme (PDB code: 1F8M). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of designed NCEs were expected to have a pharmacokinetic profile similar to their drug. Overall, it is important to state that the methodology used for pharmacophore optimization using 2D, 3D, G-QSAR, and molecular docking ADMET research works was discovered to be extremely accurate.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"425 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139204808","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 : 2023-11-30DOI: 10.25004/ijpsdr.2023.150607
Prabhat K Das, J. Vaghela, Nitin Deshmukh
Glycolate oxidase has long been thought to be a key player in the formation of oxalate accumulation in the human body. Both the endogenous synthesis of oxalate and clinically identified targets for the therapy of primary hyperoxaluria are affected by this disorder. The role of glycolate oxidase has been investigated in order to provide additional insight into the possible molecular pathways involved. The presence of flavonoids in the ethanolic extract led to the conclusion that it was suitable following phytochemical screening. Column chromatography was used to isolate the active component using the proper solvent system. The structure of the active, separated phytoconstituents was ascertained using a variety of spectral techniques, including FTIR, NMR, and GCMS analysis. Following structure elucidation, glycolate oxidase (PDB: 2RDT) and quercetin were used as standards in molecular docking investigations. Studies on in-vitro enzyme inhibition were carried out to verify the outcome. The investigation of the isolated compound’s spectral data determined that the structure might be 4-hydroxy-3-nitro coumarin. Additional molecular docking studies were carried out using conventional standard flavonoid quercetin to speculate on the compound’s potential mechanism of action. The chemical was discovered to be effective during the inhibition of the target enzyme by occupying the majority of the amino acid active sites. In-vitro enzyme inhibition tests provided additional confirmation for the computational investigations. The isolated compound’s significant IC50 value in this study was demonstrated in comparison to standard quercetin’s efficacy. These findings supported the isolated compound’s potential mechanism of action, which involves inhibiting the enzyme glycolate oxidase in terms of its anti-urolithiasis efficacy. The study also provided justification for the compound’s potential therapeutic application in urolithiasis.
{"title":"Isolation, Characterization, In-silico and Enzyme Inhibition Studies of Bougainvillea spectabilis against a Hyperoxaluria Initiator Glycolate Oxidase","authors":"Prabhat K Das, J. Vaghela, Nitin Deshmukh","doi":"10.25004/ijpsdr.2023.150607","DOIUrl":"https://doi.org/10.25004/ijpsdr.2023.150607","url":null,"abstract":"Glycolate oxidase has long been thought to be a key player in the formation of oxalate accumulation in the human body. Both the endogenous synthesis of oxalate and clinically identified targets for the therapy of primary hyperoxaluria are affected by this disorder. The role of glycolate oxidase has been investigated in order to provide additional insight into the possible molecular pathways involved. The presence of flavonoids in the ethanolic extract led to the conclusion that it was suitable following phytochemical screening. Column chromatography was used to isolate the active component using the proper solvent system. The structure of the active, separated phytoconstituents was ascertained using a variety of spectral techniques, including FTIR, NMR, and GCMS analysis. Following structure elucidation, glycolate oxidase (PDB: 2RDT) and quercetin were used as standards in molecular docking investigations. Studies on in-vitro enzyme inhibition were carried out to verify the outcome. The investigation of the isolated compound’s spectral data determined that the structure might be 4-hydroxy-3-nitro coumarin. Additional molecular docking studies were carried out using conventional standard flavonoid quercetin to speculate on the compound’s potential mechanism of action. The chemical was discovered to be effective during the inhibition of the target enzyme by occupying the majority of the amino acid active sites. In-vitro enzyme inhibition tests provided additional confirmation for the computational investigations. The isolated compound’s significant IC50 value in this study was demonstrated in comparison to standard quercetin’s efficacy. These findings supported the isolated compound’s potential mechanism of action, which involves inhibiting the enzyme glycolate oxidase in terms of its anti-urolithiasis efficacy. The study also provided justification for the compound’s potential therapeutic application in urolithiasis.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139198495","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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