Discovery, lead identification and exploration of potential oxadiazole derivatives in targeting STAT3 as anti-cancer agents.

Autor: Panwar V; Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229 India., SenGupta S; Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229 India., Kumar S; Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029 India., Singh PP; Department of Chemistry, United College of Engineering & Research, Prayagraj, 211010 India., Kumar A; Mahavir Cancer Sansthan & Research Centre, Patna, Bihar- 801505 India., Azizov S; Laboratory of Biological Active Macromolecular Systems, Institute of Bioorganic Chemistry, Academy of Sciences Uzbekistan, 100125 Tashkent, Uzbekistan.; Faculty of Life Sciences, Pharmaceutical Technical University, 100084 Tashkent, Uzbekistan., Gupta MK; Department of Chemistry, Central University of Haryana, Mahendergarh, 123031 Haryana India., Kumar D; Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229 India.
Jazyk: angličtina
Zdroj: In silico pharmacology [In Silico Pharmacol] 2024 Sep 14; Vol. 12 (2), pp. 83. Date of Electronic Publication: 2024 Sep 14 (Print Publication: 2024).
DOI: 10.1007/s40203-024-00261-w
Abstrakt: Oxadiazoles an important heterocyclic scaffold of medicinal importance in the field of drug discovery. In the study, a library of oxadiazole based compounds was selected for screening against STAT-3 as anti-cancer target. STAT3 is a potential target of interest in cancer therapy. A total of 544 screened library of compounds was subjected to molecular docking against STAT-3 (6NJS and 6NQU). The compounds with good dock score and binding interations were further subjected to in-silico ADME analysis followed by toxicity estimation. A total of 141 hits were selected against 6NJS and 50 hits against 6NQU and further screened for kinetic properties and drug likeliness. The compounds were screened on the basis of physico-chemical properties, solubility, gastrointestinal absorption, BBB permeability, synthetic accessibility, Lipinski and other violations. Best compounds obtained after ADME analysis were further subjected for toxicity analysis. Carcinogenecity, mutagenicity, Ames and other important parameters were considered for toxicity based screening. The best leads thus obtained (compound 114 and 40) were further subjected to molecular dynamics against the respective target proteins. MD simulations were run to access the stability of C-114 and C-40 along with the dynamic behaviour of both complexes for about 100 ns and shows good stability with the proteins.
Competing Interests: Conflict of interestThe authors declare no competing interests.
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Databáze: MEDLINE
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