In silico Design and Synthesis of Some New Imidazole Derivatives for Tuberculosis

Jena, Ashutosh; Prakashraj, C.; Chagaleti, Bharath Kumar; Kathiravan, M. K.; Kumar, B. Shantha

doi:10.59467/ijhc.2023.33.43

Cited by 4 publications

(3 citation statements)

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“…Visualization of the docked complexes was done by using the Biovia molecular discovery studio visualizer. 19 Based on the experimental evidence and the validation report like resolution, Ramachandran outliers and side chain outliers, the pdb 2X08 was found to be selective. Moreover, the co-crystallized ligand present in the protein was found to be ascorbate which is an excellent standard that can be comparatively studied against the synthesized molecules.…”

Section: Methodsmentioning

confidence: 93%

2,4-Substituted Oxazolones: Antioxidant Potential Exploration

Thanvi,

Chagaleti,

Srimathi R

et al. 2024

J. Young Pharm.

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Background: This study focuses on the development of a novel and environmentally friendly synthetic methodology for the production of a series of six 4-benzylidene-2-phenyloxazol-5(4H)-one derivative (M1-M6). The approach involves a one-pot procedure utilizing hippuric acid, fused sodium acetate and various substituted aromatic aldehydes in the presence of acetic anhydride. Purpose: The primary objective is to explore the potential antioxidant properties of the synthesized compounds and contribute to the understanding of azlactones as promising antioxidants. The study integrates experimental synthesis with in silico methodologies to comprehensively characterize the chemical and biological properties of the derivatives. Materials and Methods:The synthesis process employed a combination of hippuric acid, fused sodium acetate and substituted aromatic aldehydes in a one-pot procedure. The chemical structures of the derivatives were characterized and validated through in silico techniques, including docking studies, drug-likeness assessments, bioactivity predictions, ADME profiling and toxicity evaluations. Results: The in silico analyses provided insights into the molecular interactions, pharmacokinetic properties and safety profiles of the synthesized compounds. In vitro antioxidant potential was systematically investigated using the DPPH method, with compounds M 3 and M 5 demonstrating significant antioxidant activity at a concentration 40 µg/ mL showing (88% inhibition) and (85.7% inhibition) respectively, surpassing ascorbic acid as the reference standard. Conclusion: This study successfully explores azlactones as potential antioxidants, combining experimental synthesis and in silico methodologies to characterize the chemical and biological properties of the synthesized derivatives. The notable antioxidant activity of compounds M 3 and M 5 positions them as promising candidates for further investigation. The findings establish a foundation for future research and development of these compounds in potential antioxidant-related therapeutic interventions.

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Section: Methodsmentioning

confidence: 93%

2,4-Substituted Oxazolones: Antioxidant Potential Exploration

Thanvi,

Chagaleti,

Srimathi R

et al. 2024

J. Young Pharm.

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“…The pharmacological impact of a drug is determined by its physical and chemical attributes, including molecular weight, partition coe cient, number of rotatable bonds, topological polar surface area, hydrogen bond acceptors and donors, among other parameters. Interestingly, the topological polar surface area plays a crucial role in de ning drug absorption pathways, including blood-brain barrier penetration, intestinal absorption, bioavailability, and Caco-2 permeability [55][56][57].…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

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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“…The selection of the active site is mainly based on the size of the active site and interactions of the Cocrystal residues. [66][67][68] The 30 novel designed ligands were drawn and prepared by MOE, and energy minimization was done. Once the MOE docking protocol's placement scoring and scoring function were combined, the docking procedure was run to simulate the molecular docking of native ligands to the target protein.…”

Section: Molecular Dockingmentioning

confidence: 99%