Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines

2009 ◽  
Vol 14 (2) ◽  
pp. 285-305 ◽  
Author(s):  
Atul T. Manvar ◽  
Raghuvir R. S. Pissurlenkar ◽  
Vijay R. Virsodia ◽  
Kuldip D. Upadhyay ◽  
Dinesh R. Manvar ◽  
...  
Keyword(s):  
3D Qsar ◽  
Antitubercular Activity ◽  
Qsar Study

In Silico (3D-QSAR) Designed, Study, Synthesis and Anti-tubercular Evaluation of Pyrazolo-Pyrimidine Derivatives

2020 ◽  
Vol 18 (2) ◽  
pp. 135-143
Author(s):  
Pratiksha Chhatbar ◽  
Kaushik Pambhar ◽  
Vijay Khedkar ◽  
Anamik Shah ◽  
Ranjan Khunt
Keyword(s):  
3D Qsar ◽  
Antitubercular Activity ◽  
Tuberculosis H37rv ◽  
Eukaryotic Cells ◽  
Antitubercular Agents ◽  
Pyrimidine Derivatives ◽  
Qsar Study ◽  
Chemical Structures ◽  
Microbial Study

Background: A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole-pyrimidine derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. Objective: The current research aimed to synthesize and evaluateed pyrazole-pyrimidine based antitubercular agents by an in vitro microbial study based on our previously reported 3D-QSAR. Methods: The designed molecules were synthesised via chalcone intermediate and cyclisation using guanidine and urea. The molecules were then characterized by various spectroscopic methods like IR, MASS, 1H-NMR, 13C-NMR and in vitro evaluation against M. tuberculosis H37Rv. They were further evaluated under anaerobic condition and their intracellular assay was studied. The compounds were further examined for cytotoxicity towards eukaryotic cells. Results: Compounds 3a, 3c and 3i were found to be the most effective against M. tuberculosis H37Rv, with IC50 of 16μM, 13μM and 15μM, respectively. Conclusion: The designed strategy, to enhance the antitubercular activity against M. tuberculosis H37Rv, was proved fruitful. On considering the overall data, the promising results would be useful to design the next target with improved efficacy and potency of compounds for further medicinal importance.

scholarly journals In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1753 ◽  
Author(s):  
Joanna Ziemska ◽  
Jolanta Solecka ◽  
Małgorzata Jarończyk
Keyword(s):  
Leucine Aminopeptidase ◽  
Three Dimensional ◽  
3D Qsar ◽  
In Vivo Studies ◽  
Statistical Parameters ◽  
Qsar Study ◽  
Lipinski’S Rule ◽  
Aminopeptidase Inhibitors

Cancers are the leading cause of deaths worldwide. In 2018, an estimated 18.1 million new cancer cases and 9.6 million cancer-related deaths occurred globally. Several previous studies have shown that the enzyme, leucine aminopeptidase is involved in pathological conditions such as cancer. On the basis of the knowledge that isoquinoline alkaloids have antiproliferative activity and inhibitory activity towards leucine aminopeptidase, the present study was conducted a study which involved database search, virtual screening, and design of new potential leucine aminopeptidase inhibitors with a scaffold based on 3,4-dihydroisoquinoline. These compounds were then filtered through Lipinski’s “rule of five,” and 25 081 of them were then subjected to molecular docking. Next, three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed for the selected group of compounds with the best binding score results. The developed model, calculated by leave-one-out method, showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.997) and q2 (0.717). Further, 35 compounds were identified to have an excellent predictive reliability. Finally, nine selected compounds were evaluated for drug-likeness and different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Our methodology suggested that compounds with 3,4-dihydroisoquinoline moiety were potentially active in inhibiting leucine aminopeptidase and could be used for further in-depth in vitro and in vivo studies.

3D QSAR study, synthesis, and in vitro evaluation of (+)-5-FBVM as potential PET radioligand for the vesicular acetylcholine transporter (VAChT)

2010 ◽  
Vol 18 (21) ◽  
pp. 7659-7667 ◽  
Author(s):  
Mitja Kovac ◽  
Sylvie Mavel ◽  
Winnie Deuther-Conrad ◽  
Nathalie Méheux ◽  
Jana Glöckner ◽  
...  
Keyword(s):  
3D Qsar ◽  
Vesicular Acetylcholine Transporter ◽  
Qsar Study ◽  
In Vitro Evaluation

scholarly journals Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Nopol-Derived 1,3,4-Thiadiazole-Thiourea Compounds

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1708
Author(s):  
Ming Chen ◽  
Wen-Gui Duan ◽  
Gui-Shan Lin ◽  
Zhong-Tian Fan ◽  
Xiu Wang
Keyword(s):  
Antifungal Activity ◽  
Alternaria Solani ◽  
3D Qsar ◽  
Qsar Model ◽  
Gibberella Zeae ◽  
Cercospora Arachidicola ◽  
Qsar Study ◽  
Structure Activity ◽  
Better Than

A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. All the target compounds exhibited better antifungal activity against P. piricola, C. arachidicola, and A. solani. Compound 6j (R = m, p-Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds 6c (R = m-Me Ph), 6q (R = i-Pr), and 6i (R = p-Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Moreover, compounds 6h (R = m-Cl Ph) and 6n (R = o-CF3 Ph) held inhibition rates of 80.6% and 79.0% against C. arachidicola and G. zeae, respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against A. solani, analysis of the three-dimensional quantitative structure–activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r2 = 0.992, q2 = 0.753) has been established. Furthermore, some intriguing structure–activity relationships were found and are discussed by theoretical calculation.

scholarly journals Quantitative Structure–Activity Relationships of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5249
Author(s):  
Friederike M. Wunsch ◽  
Bernhard Wünsch ◽  
Freddy A. Bernal ◽  
Thomas J. Schmidt
Keyword(s):  
3D Qsar ◽  
Structure Activity Relationship ◽  
Structural Features ◽  
Field Analysis ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Qsar Study ◽  
Activity Data ◽  
Structure Activity

On the basis of the finding that various aminoalkyl-substituted chromene and chromane derivatives possess strong and highly selective in vitro bioactivity against Plasmodium falciparum, the pathogen responsible for tropical malaria, we performed a structure–activity relationship study for such compounds. With structures and activity data of 52 congeneric compounds from our recent studies, we performed a three-dimensional quantitative structure–activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) approach as implemented in the Open3DQSAR software. The resulting model displayed excellent internal and good external predictive power as well as good robustness. Besides insights into the molecular interactions and structural features influencing the antiplasmodial activity, this model now provides the possibility to predict the activity of further untested compounds to guide our further synthetic efforts to develop even more potent antiplasmodial chromenes/chromanes.

Synthesis, In Vitro Antitubercular Activity and 3D-QSAR of Novel Quinoxaline Derivatives

2011 ◽  
Vol 78 (6) ◽  
pp. 988-998 ◽  
Author(s):  
Ayarivan Puratchikody ◽  
Ramalakshmi Natarajan ◽  
Mohanapriya Jayapal ◽  
Mukesh Doble
Keyword(s):  
3D Qsar ◽  
Antitubercular Activity ◽  
Quinoxaline Derivatives

scholarly journals Synthesis of Bioactive Compounds from 3-Carene (II): Synthesis, Antifungal Activity and 3D-QSAR Study of (Z)- and (E)-3-Caren-5-One Oxime Sulfonates

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 477 ◽  
Author(s):  
Guo-Qiang Kang ◽  
Wen-Gui Duan ◽  
Gui-Shan Lin ◽  
You-Pei Yu ◽  
Xiao-Yu Wang ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Three Dimensional ◽  
Alternaria Solani ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Cercospora Arachidicola ◽  
Qsar Study ◽  
In Vitro Antifungal Activity

A series of novel (Z)- and (E)-3-caren-5-one oxime sulfonates were designed and synthesized in search of potent antifungal agents. The structures of the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, and ESI-MS. The in vitro antifungal activity of the target compounds was preliminarily evaluated against Cercospora arachidicola, Physalospora piricola, Alternaria solani, Rhizoeotnia solani, Bipolaris maydis and Colleterichum orbicalare at 50 µg/mL. The bioassay results indicated that the target compounds exhibited the best antifungal activity against P. piricola, in which compounds 4b, 4f, 4m, 4e, 4j, 4l, 4y, 4d, and 4p had excellent inhibition rates of 100%, 100%, 100%, 92.9%, 92.9%, 92.9%, 92.9%, 85.7%, and 85.7%, respectively, showing much better antifungal activity than that of the commercial fungicide chlorothanil. Both the compounds 4y and 4x displayed outstanding antifungal activity of 100% against B. myadis, and the former also displayed outstanding antifungal activity of 100% against R. solani. In order to design more effective antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r2 = 0.990, q2 = 0.569) has been established.

scholarly journals In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c)

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259348
Author(s):  
Ruben Cloete ◽  
Mohd Shahbaaz ◽  
Melanie Grobbelaar ◽  
Samantha L. Sampson ◽  
Alan Christoffels
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sodium Salt ◽  
In Silico ◽  
Drug Target ◽  
3D Qsar ◽  
Active Site Residues ◽  
Chemical Library ◽  
Qsar Study ◽  
Promising Alternative

Nicotinamide-nucleotide adenylyl transferase (Rv2421c) was selected as a potential drug target, because it has been shown, in vitro, to be essential for Mycobacterium tuberculosis growth. It is conserved between mycobacterium species, is up-regulated during dormancy, has a known 3D crystal structure and has no known human homologs. A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject tovirtual ligand screening against the Prestwick Chemical Library and the ZINC database, which yielded 155 potential hit molecules. Of the 155 compounds identified five were pursued further using an IC50 based 3D-QSAR study. The 3D-QSAR model validated the inhibition properties of the five compounds based on R2 value of 0.895 and Q2 value of 0.944 compared to known inhibitors of Rv2421c. Higher binding affinities was observed for the novel ZINC13544129 and two FDA approved compounds (Novobiocin sodium salt, Sulfasalazine). Similarly, the total interaction energy was found to be the highest for Cromolyn disodium system (-418.88 kJ/mol) followed by Novobiocin (-379.19 kJ/mol) and Sulfasalazine with (-330.13 kJ/mol) compared to substrate DND having (-185.52 kJ/mol). Subsequent in vitro testing of the five compounds identified Novobiocin sodium salt with activity against Mycobacterium tuberculosis at 50 μM, 25μM and weakly at 10μM concentrations. Novobiocin salt interacts with a MG ion and active site residues His20, Thr86, Gly107 and Leu164 similar to substrate DND of Mycobacterium tuberculosis Rv2421c. Additional in silico structural analysis of known Novobiocin sodium salt derivatives against Rv2421c suggest Coumermycin as a promising alternative for the treatment of Mycobacterium tuberculosis based on large number of hydrogen bond interactions with Rv2421c similar in comparison to Novobiocin salt and substrate DND.

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