In-silico investigation and drug likeliness studies of benzimidazole congeners: The new face of innovation

Thapa, Shankar; Nargund, Shachindra L.; Biradar, Mahalakshmi Suresha; Banerjee, Janmajay; Karati, Dipanjan

doi:10.1016/j.imu.2023.101213

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Yoon et al reported that compounds 1c and 1d showed excellent potency against Mtb-H37RV with MIC of <0.2 μ M [ 35 ]. In addition, several substituted benzimidazoles have demonstrated favorable oral bioavailability and safety profiles based on in silico studies [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Thapa,

Biradar,

Nargund

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, 1H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/mL) and 8 (MIC = 0.8 g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of −7.36 and −7.17 kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Thapa,

Biradar,

Nargund

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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“…To validate the docking interaction, the redocking method was employed and the root mean square deviation (RMSD) value was calculated using PyMol 2.5.4 software ( https://pymol.org/ ). The RMSD value less than 2 Å was considered as best fitted model [ 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

In Silico and In Vitro Studies of Antibacterial Activity of Cow Urine Distillate (CUD)

Pant,

Thapa,

Dahal

et al. 2024

Evidence-Based Complementary and Alternative Medicine

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Cow urine distillate (CUD) is a traditional Indian medicine used to treat various diseases, including bacterial infections. However, there is limited evidence to support its use as a medicine, and its safety and efficacy have not been thoroughly studied. In this study, we evaluated the antibacterial activity of CUD against five bacterial strains using in vitro and in silico approaches. In vitro experiments showed that CUD has significant antibacterial activity against all tested strains with a zone of inhibition (ZOI) ranging from 13 to 24 mm and minimum inhibitory concentration (MIC) values ranging from 12.5 to 50 µg/ml. The results indicated that the 15% concentration of CUD displayed the highest antibacterial activity against Staphylococcus aureus and Salmonella typhi. To further investigate the antibacterial mechanism of CUD, we performed in silico docking studies of the active compounds of CUD with bacterial proteins involved in protein synthesis. Our results showed that 2-hydroxycinnamic acid (ΔG = −6.9 kcal/mol) and ferulic acid (ΔG = −6.8 kcal/mol) exhibited the best docking scores with the targeted proteins (DNA gyrase, PDBID: 4KFG). The hydrogen bonding interaction with amino acids Val71 and Asp73 was found to be crucial for their antibacterial activity.

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“…Yoon et al reported that, compounds 1c and 1d showed excellent potency against Mtb-H37RV with MIC of < 0.2 𝜇M [36]. In addition, several substituted benzimidazoles have demonstrated favorable oral bioavailability and safety pro les based on in-silico studies[37].…”

mentioning

confidence: 99%

Synthesis, molecular docking, molecular dynamic simulation studies, and anti-tubercular activity evaluation of substituted benzimidazole derivatives

Thapa

Biradar

Nargund³

et al. 2023

Preprint

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Tuberculosis, colloquially referred to as TB, is a highly prevalent bacterial infection that persists as a substantial global health concern. The present article centers its attention on the comprehensive exploration of the synthesis, molecular docking, and molecular dynamic simulation investigations pertaining to substituted benzimidazole derivatives. Additionally, a meticulous assessment of their anti-TB activities is conducted. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FT-IR, 1H-NMR, and Mass spectra. The Microplate Alamar Blue Assay (MABA) was used to evaluate the anti-mycobacterial activity of synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/ml) and 8 (MIC = 0.8 g/ml) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard (Isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of -7.36 and − 7.17 kcal/mol, respectively. Both substances were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

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In-silico investigation and drug likeliness studies of benzimidazole congeners: The new face of innovation

Cited by 4 publications

References 36 publications

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

In Silico and In Vitro Studies of Antibacterial Activity of Cow Urine Distillate (CUD)

Synthesis, molecular docking, molecular dynamic simulation studies, and anti-tubercular activity evaluation of substituted benzimidazole derivatives

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