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Volume 22, Issue 1
  • ISSN: 1570-1638
  • E-ISSN: 1875-6220

Abstract

Background

A novel series of 1,3,4‒oxadiazole connected to derivatives of quinazolinone ( and ) 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: 1H & 13C). 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 , and demonstrated encouraging cytotoxicity findings against HCT‒116 and HepG2 cancer cell lines, with IC values ranging from 3.85 to 19.43 μM. Compounds , , and were the most potent inhibitors of Topo II with IC values of 15.18, 17.55, and 12.59 μM, respectively. Additionally, the docked compound 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 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.

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2025-01-01
2024-11-26

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New 1,3,4‒oxadiazole Quinazolines as Potential Anticancer Agents: Design, Synthesis, Biological Evaluation, and In silico Studies
Current Drug Discovery Technologies 22, E090424228867 (2025); https://doi.org/10.2174/0115701638282655240402042126
/content/journals/cddt/10.2174/0115701638282655240402042126
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  • Article Type:     Research Article
Keyword(s): 1,3,4‒Oxadiazole; 2-amino-3-methylbenzoic acid; ADMET; antiproliferative activity; formamide; topo II inhibitors

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