New 1,3,4‒oxadiazole Quinazolines as Potential Anticancer Agents: Design, Synthesis, Biological Evaluation, and In silico Studies.

Autor: Gujja V; Department of Chemistry, Gitam Deemed to be University, Hyderabad campus, Rudraram, Sangareddy, Hyderabad, 502329, Telangana, India., Sadineni K; Department of Chemistry, Gitam Deemed to be University, Hyderabad campus, Rudraram, Sangareddy, Hyderabad, 502329, Telangana, India., Koppula SK; Department of Chemistry, Gitam Deemed to be University, Hyderabad campus, Rudraram, Sangareddy, Hyderabad, 502329, Telangana, India., Basireddy A; Department of Chemistry, School of Applied Sciences and Humanities, VFSTR (Deemed to be University), Vadlamudi, Guntur, Andhra Pradesh, 522213, India.; Department of Chemistry, Malla Reddy Institute of Technology and Science, Maisammaguda, Dulapally, Hyderabad, Telangana, 500100, India., Venkanna B; Centre for Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, 500085, Telangana, India., Gunda SK; Bioinformatics Division, PGRRCDE, Osmania University, Tarnaka, Hyderabad, 500007, Telangana, India.
Jazyk: angličtina
Zdroj: Current drug discovery technologies [Curr Drug Discov Technol] 2025; Vol. 22 (1), pp. e090424228867.
DOI: 10.2174/0115701638282655240402042126
Abstrakt: Background: A novel series of 1,3,4‒oxadiazole connected to derivatives of quinazolinone (7a-e and 8a-f) was synthesized in the current investigation, and its anticancer and Topoisomerase‒ II inhibitory activity was evaluated.
Objective: These findings inspired the design, synthesis, and biological analysis of these 1,3,4‒oxadiazole-quinazolinone analogues as antiproliferative Topo‒II inhibitors.
Methods: The novel compound structures were determined using mass spectrometry and spectral methods (IR, NMR: 1 H & 13 C). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colourimetric assay has been used to evaluate the anticancer efficacy of these drugs, and Autodock 4.2 provides a description of the docking results. For the more active members, additional biological tests, such as the Topo‒II inhibition experiment, were performed. These compounds' physicochemical and ADMET characteristics were examined in more detail.
Results: In the experiment for antiproliferative activity, compounds 7d, 7e, 8c, 8e, and 8f demonstrated encouraging cytotoxicity findings against HCT‒116 and HepG2 cancer cell lines, with IC 50 values ranging from 3.85 to 19.43 μM. Compounds 7d, 7e, and 8e were the most potent inhibitors of Topo II with IC 50 values of 15.18, 17.55, and 12.59 μM, respectively. Additionally, the docked compound 8c showed the strongest conventional hydrogen bonds among the residues Leu507(B), Asn508(B), Asn520(B), and Glu522(B) in the Human topoisomerase‒IIβ active site in the DNA complex (4G0U) when compared to the findings of docking experiments.
Conclusion: New findings have discovered the fact that fused 1,3,4‒oxadiazole bearing quinazolinone contributed great significance in the field of medicinal chemistry due to their diverse biological properties. Finally, the in silico pharmacokinetic profile of all the synthesized derivatives was estimated using SwissADME, where some of the compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation. The result of this activity advises that with a simple modification in structure, a potent anticancer agent can be generated with good efficacy.
(Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze: MEDLINE
Externí odkaz: