In-silico design and ADMET predictions of some new imidazo[1,2-a]pyridine-3-carboxamides (IPAs) as anti-tubercular agents
| Autor: | Shola Elijah Adeniji, Niloy Das, Alhassan Kabiru Usman, Ahmad Muhammad Sani, Mustapha Abdullahi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Pulmonary and Respiratory Medicine Drug media_common.quotation_subject In silico Infectious and parasitic diseases RC109-216 Article Mycobacterium tuberculosis In-silico design chemistry.chemical_compound Diseases of the respiratory system Pyridine medicine Molecular interactions Tuberculosis Pharmacokinetics ADME media_common Hydrogen bond biology RC705-779 business.industry Isoniazid Ligand (biochemistry) biology.organism_classification Combinatorial chemistry Infectious Diseases Binding affinity chemistry Docking (molecular) business medicine.drug |
| Zdroj: | Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, Vol 25, Iss, Pp 100276-(2021) Journal of Clinical Tuberculosis and Other Mycobacterial Diseases |
| ISSN: | 2405-5794 |
| Popis: | Tuberculosis (TB) is one of the leading infectious diseases worldwide even with the ravaging COVID-19 pandemic in recent times. This mandated further search and exploration of more possible anti-TB drug candidates against M. tuberculosis strains. As an extension of our previous work on the homology modeled cytochrome b subunit of the bc1 complex (QcrB) of Mycobacterium tuberculosis, an in-silico design was carried out in order to further explore more newly potential anti-TB compounds. Ligand 26 was selected as the lead template (scaffold A) based on our previous docking results and its less bulky structure. Successively, eight (8) new ligands (A1-A8) were designed with better binding affinities in comparison to the scaffold template (-6.8 kcal/mol) and isoniazid standard drug (-6.00 kcal/mol) respectively. In addition, three (3) designed ligands namely, A6, A2, and A7 with higher binding affinities were validated via ADME and toxicity prediction analysis, and the results showed zero violations of Lipinski rules with similar bioavailability, and high rate in gastrointestinal absorption, while toxicity parameters such as carcinogenicity and cytotoxicity were all predicted as non-toxic (inactiveness). The designed IPA compounds in the present study could serve as a promising gateway that could help the medicinal and synthetic chemist in the exploration of a new set of derivatives as anti-TB agents. Therefore, this research strongly recommends further experimental consideration of the newly designed IPA compounds through synthesis, in-vitro and in-vivo studies to validate the theoretical findings. |
| Databáze: | OpenAIRE |
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