3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors

Singh, Udghosh; Gangwal, Rahul P.; Dhoke, Gaurao V.; Prajapati, Rameshwar; Damre, Mangesh V.; Sangamwar, Abhay T.

doi:10.1016/j.arabjc.2012.10.023

Cited by 13 publications

(2 citation statements)

References 27 publications

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“…In the field of drug discovery, the prediction of interactions between molecules and their targets has a great importance. One can easily find out the mechanisms of selectivity by the docking of molecules with protein targets. − In this work, the activities of anacardic derivatives were screened out against the target cyclin-dependent kinase 2 (PDB ID: 1w98). Cyclin-dependent kinase 2, also known as cell-division protein kinase 2, is an enzyme usually found in humans.…”

Section: Resultsmentioning

confidence: 99%

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives

et al. 2020

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Anacardic acid (AA) and its derivatives are wellknown for their therapeutic applications ranging from antitumor, antibacterial, antioxidant, anticancer, and so forth. However, their poor pharmacokinetic and safety properties create significant hurdles in the formulation of the final drug molecule. As a part of our endeavor to enhance the potential and exploration of the anticancer activities, a detailed study on the properties of selected AA derivatives was performed in this work. A comprehensive analysis of the drug-like properties of 100 naturally occurring AA derivatives was performed, and the results were compared with certain marketed anticancer drugs. The work focused on the understanding of the interplay among eight physicochemical properties. The relationships between the physicochemical properties, absorption, distribution, metabolism, and excretion attributes, and the in silico toxicity profile for the set of AA derivatives were established. The ligand efficacy of the finally scrutinized 17 AA derivatives on the basis of pharmacokinetic properties and toxicity parameters was further subjected to dock against the potential anticancer target cyclin-dependent kinase 2 (PDB ID: 1W98). In the docked complex, the ligand molecules (AA derivatives) selectively bind with the target residues, and a high binding affinity of the ligand molecules was ensured by the full fitness score using the SwissDock Web server. The BOILED-Egg model shows that out of 17 scrutinized molecules, 3 molecules exhibit gastrointestinal absorption capability and 14 molecules exhibit permeability through the blood−brain barrier penetration. The analysis can also provide some useful insights to chemists to modify the existing natural scaffolds in designing new anacardic anticancer drugs. The increased probability of success may lead to the identification of drug-like candidates with favorable safety profiles after further clinical evaluation.

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Section: Resultsmentioning

confidence: 99%

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives

et al. 2020

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“…Molecular docking technology can effectively explore the interaction between an enzyme and ligands. 29 Docking and scoring technology is applied to drug discovery for predicting the biological activity. Generally, van der Waals forces, hydrogen bonds, hydrophobic interactions, and electrostatic interactions are regarded as the primary factors in a docking study.…”

Section: Molecular Dockingmentioning

confidence: 99%

Molecular modeling studies of HIV-1 non-nucleoside reverse transcriptase inhibitors using 3D-QSAR, virtual screening, and docking simulations

et al. 2019

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Acquired immunodeficiency syndrome (AIDS) is a significant human health threat around the world and therefore, the study of anti-HIV drug design has become an important task for today's society. In this paper, a three-dimensional quantitative structure-activity relationships study (3D-QSAR) was conducted on 72 HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) using Topomer comparative molecular field analysis (Topomer CoMFA). The multiple correlation coefficients of fitting, cross-validation, and external validation were 0.899, 0.788 and 0.942, respectively. The results indicated that the obtained model had both a favorable estimation stability and a good prediction capability. Topomer Search was used to search appropriate R groups from the ZINC database, Thereby, 14 new compounds were designed, and 12 of the new compounds were predicted to be more active than the template molecule. These results strongly suggest that the Topomer search was effective in screening and could be a useful guide in the design of new HIV-1 drugs. The ligands of the template molecule and the new designed compounds were used for molecular docking to study the interaction of these compounds with the protein receptor. The results showed that the ligands would generally form hydrogen-bonding interactions with the residues Ala28, Asp29, Gly49 and Ile50 of the protein receptor, thereby providing additional insights for the designing of even more effective drugs.

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Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach

et al. 2013

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Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis. Finally, three novel compounds with diverse scaffolds were selected as potential starting points for the design of novel dual ACC inhibitors.

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3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors

Cited by 13 publications

References 27 publications

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives

Molecular modeling studies of HIV-1 non-nucleoside reverse transcriptase inhibitors using 3D-QSAR, virtual screening, and docking simulations

Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach

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