Quantitative structure activity relationship (QSAR) modeling study of some novel thiazolidine 4-one derivatives as potent anti-tubercular agents

Moulishankar, Anguraj; Thirugnanasambandam, Sundarrajan

doi:10.1080/10799893.2023.2281671

Cited by 8 publications

(2 citation statements)

References 51 publications

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“…Similarly, Discovery Studio was used to convert the format of compound 3 and potent inhibitors from sdf to pdb format after minimizing their energy via Chem3D Pro 12.0.2.1076. Chem3D Pro 12.0.2.1076 utilizes Merck Molecular Force Field 2 (MM2) algorithm that iteratively adjusts the coordinates of atoms in the molecule to minimize its energy ( Al Azzam et al, 2022 ; Moulishankar and Thirugnanasambandam, 2023 ). Afterward, AutoDockTools 1.5.7 was utilized to construct pdbqt files of the receptor (4H9M) and potent inhibitors followed by the formation of a grid box encompassing a druggable binding site ( Fatima et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Akash,

Zaib,

Ahmad

et al. 2024

Front. Chem.

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Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of −8.0 (5b) and −8.1 (7e) kcal/mol. The binding energy of thiourea was −2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and −6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

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Section: Methodsmentioning

confidence: 99%

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Akash,

Zaib,

Ahmad

et al. 2024

Front. Chem.

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“…Following this dataset division, the QSAR model was constructed employing the multiple linear regression (MLR) method and generally validated according to the chemometric approach [41]. This methodology substantiates the direct correlation between the dependent variable Y and the independent variable X, represented by molecular descriptors [42,43]. In multiple linear regression (MLR) analysis, the mean of the dependent variable Y is dependent on X (descriptor).…”

Section: Qsar Model Developmentmentioning

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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Identification of novel DNA gyrase inhibitor by combined pharmacophore modeling, QSAR analysis, molecular docking, molecular dynamics, ADMET and DFT approaches

Moulishankar,

Sankaranarayanan,

Thirugnanasambandam

et al. 2024

Acta Tropica

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Quantitative structure activity relationship (QSAR) modeling study of some novel thiazolidine 4-one derivatives as potent anti-tubercular agents

Cited by 8 publications

References 51 publications

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

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

Identification of novel DNA gyrase inhibitor by combined pharmacophore modeling, QSAR analysis, molecular docking, molecular dynamics, ADMET and DFT approaches

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