Title:New 1,3,4‒oxadiazole Quinazolines as Potential Anticancer Agents: Design, Synthesis, Biological Evaluation, and In silico Studies
Volume: 22
Issue: 1
Author(s): Venkanna Gujja*, Kumaraswamy Sadineni, Shiva Kumar Koppula*, Avanthi Basireddy, Banothu Venkanna and Shravan Kumar Gunda
Affiliation:
- Department of Chemistry, Gitam Deemed to be University, Hyderabad campus, Rudraram, Sangareddy, Hyderabad,
502329, Telangana, India
- Department of Chemistry, Gitam Deemed to be University, Hyderabad campus, Rudraram, Sangareddy, Hyderabad,
502329, Telangana, India
Keywords:
1, 3, 4‒Oxadiazole, 2-amino-3-methylbenzoic acid, formamide, antiproliferative activity, topo II inhibitors, ADMET.
Abstract:
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: 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 7d, 7e, 8c, 8e, and 8f demonstrated
encouraging cytotoxicity findings against HCT‒116 and HepG2 cancer cell lines, with IC50
values ranging from 3.85 to 19.43 μM. Compounds 7d, 7e, and 8e were the most potent inhibitors
of Topo II with IC50 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.
