Molecular dynamics simulation approach of hybrid chalcone–thiazole complex derivatives for DNA gyrase B inhibition: lead generation

Patan, Afroz; M, Vijey Aanandhi; Gopinath, Pushparathinam

doi:10.1039/d3ra00732d

Cited by 8 publications

(2 citation statements)

References 72 publications

(96 reference statements)

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“…These compounds emerge as promising leads for targeting CDK2 in the development of groundbreaking cancer therapies.This study harnesses the power of quantitative structure-activity relationship (QSAR) analyses using state-of-the-art QSARINS software coupled with molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions and dynamic studies to comprehensively explore the intricate molecular landscape of pyrazolopyrimidine-based compounds. QSARINS is a computational tool that facilitates the development of a robust model capable of designing new molecules with enhanced anticancer activity [21,22].Most of the reported cancer drugs structurally have either pyrazole or pyrimidine moieties [23]. Pyrazolopyrimidines (PPs), which are nitrogen-fused heterocyclic rings, are recognized as bioisosteres of adenine and play crucial roles in various cellular processes [24,25].…”

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confidence: 99%

“…This study harnesses the power of quantitative structure-activity relationship (QSAR) analyses using state-of-the-art QSARINS software coupled with molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions and dynamic studies to comprehensively explore the intricate molecular landscape of pyrazolopyrimidine-based compounds. QSARINS is a computational tool that facilitates the development of a robust model capable of designing new molecules with enhanced anticancer activity [21,22].…”

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confidence: 99%

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Molecular modeling studies of Pyrazolopyrimidine Derivatives as potent Cyclin Dependent Kinase-2 inhibitors

Chagaleti,

2024

Preprint

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This study addresses the pressing need for innovative cancer treatments in the face of global challenges posed by the widespread occurrence of cancer and increasing treatment resistance. The study looks at cyclin-dependent kinase-2 (CDK2) and uses a methodical computer approach to find possible anticancer compounds with pyrazole and pyrimidine structures. (QSAR) quantitative structure-activity relationship has become crucial in lead optimization over the last three decades. A set of 45 pyrazolopyrimidine derivatives with known IC50 values were used to create and test models using QSARINS software. Model 4, with its high predictive performance (R2 = 0.9100, R2adj = 0.8900, LOF = 0.0394), emerges as the most reliable. The resulting QSAR model proves stable, predictive, and robust, effectively representing the original dataset. Active molecular descriptors are identified for predicting the structure-activity relationship. We used SAR analysis and model equation parameters to create sixty compounds and tested them for their predicted bioactivity using Model 4. These compounds are a series with pyrazolopyrimidine-fused piperidine and hybrid moieties, such as methanethione (20), ethenone (20), and benzamide (20). Among the designed series, 16 compounds exhibited pIC50 values exceeding 7, indicating that they were hit molecules represented as C1-C16. These obtained hit molecules undergo further screening with ADMET, molecular docking, and molecular dynamics simulations. C3 and C7, revealed in docking studies with low-energy conformations and sustained binding during simulations, consistently align their binding modes with the standard drug roscovitine. These compounds emerge as promising leads for targeting CDK2 in the development of groundbreaking cancer therapies.

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confidence: 99%

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confidence: 99%

Molecular modeling studies of Pyrazolopyrimidine Derivatives as potent Cyclin Dependent Kinase-2 inhibitors

Chagaleti,

2024

Preprint

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Computational Integration of TRPV4 Antagonists: 3D QSAR, Molecular Docking, Molecular Dynamics Simulations, ADME/Tox, and Retrosynthesis studies

Abdelilah,

Oussama,

Abdellah

et al. 2024

ChemistrySelect

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TRPV4 antagonists that could be potential drugs for treatment and management of neuropathic pain. This study was conducted to systematically design several amino derivatives of 2,4′‐dimethyl‐[4,5′‐bithiazol]‐2‐yl as antagonists. In silico computational methods, such as 3D quantitative structure‐activity relationship modeling (3D‐QSAR), molecular docking, and pharmacokinetic property assessment (ADMET), were used to discover new compounds with strong antagonistic activity. The best‐performing 3D‐QSAR model was developed using a partial least squares approach and comparative molecular similarity analysis (CoMSIA). The developed model demonstrated an excellent ability to correlate and predict properties (R2 = 0.932, Q2 = 0.620, and SEE = 0.109). It was observed that variations in biological activity were significantly influenced by interactions with steric, electrostatic, and hydrophobic fields. Molecular docking was used to validate the 3D‐QSAR methods and to explain the binding site and interactions between the most active ligands and the receptor. Based on these results, a new series of compounds was predicted. The best‐anchored molecules underwent MD simulation to confirm their dynamic behavior and stability, and they also underwent retrosynthetic analysis to assist in their synthesis.

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Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods

Yasmeen,

Chaudhary,

Khan

et al. 2024

Mol Divers

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Molecular dynamics simulation approach of hybrid chalcone–thiazole complex derivatives for DNA gyrase B inhibition: lead generation

Abstract: Compounds bearing thiazole and chalcone groups have been reported to be excellent leads for antibacterial, antitubercular and anticancer activities.

Cited by 8 publications

References 72 publications

Molecular modeling studies of Pyrazolopyrimidine Derivatives as potent Cyclin Dependent Kinase-2 inhibitors

Molecular modeling studies of Pyrazolopyrimidine Derivatives as potent Cyclin Dependent Kinase-2 inhibitors

Computational Integration of TRPV4 Antagonists: 3D QSAR, Molecular Docking, Molecular Dynamics Simulations, ADME/Tox, and Retrosynthesis studies

Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods

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