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Vol. 38 No. 7 (2026): Vol. 38, No 7 (2026)

Copyright (c) 2026 Sailu Bethala, Ramu Perumandla, Sairam Gummula, Shylaja Kotte

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Synthesis of Novel Pyrimido[1,2-c]quinazolin-4-one and Triazolo[4,3-c]quinazoline Derivatives: Anticancer Activity and Docking Interactions

https://doi.org/10.14233/ajchem.2026.36088
Ramu Perumandla
Department of Chemistry, Telangana University, Dichpally, Nizamabad-503322, India
https://orcid.org/0009-0008-8699-1365
Sairam Gummula
Department of Chemistry, Telangana University, Dichpally, Nizamabad-503322, India
https://orcid.org/0009-0007-4601-1396
Shylaja Kotte
Department of Chemistry, Mallareddy Engineering College for Women (Autonomous) Dulapally, Secundrabad-500100, India
https://orcid.org/0009-0004-0759-5075
Sailu Betala
Department of Chemistry, Telangana University, Dichpally, Nizamabad-503322, India
https://orcid.org/0000-0003-1072-6895

Corresponding Author(s) : Sailu Betala

bethalasailu@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 7 (2026): Vol. 38, No 7 (2026)

Abstract

A series of novel pyrimido[1,2-c]quinazolin-4-one and triazolo[4,3-c]quinazoline derivatives were synthesized starting from 2-amino-5-(trifluoromethyl)benzonitrile. The acidic hydrolysis of the nitrile group afforded 2-amino-6-(trifluoromethyl)benzoic acid, which subsequently underwent cyclization in the presence of formic acid to yield the corresponding quinazolinone intermediate. Treatment of this cyclised product with ethyl 2-bromoacetate produced 6-(trifluoromethyl)quinazolin-4-amine. Further condensation of this amine with various substituted ethyl 2-methyl-3-oxobutanoates furnished a series of pyrimido[1,2-c]quinazolin-4-one derivatives (5a-f). In a parallel synthetic route, 6-(trifluoromethyl)quinazolin-4(3H)-one was reacted with phosphorus oxychloride (POCl3) to generate 4-chloro-6-(trifluoro-methyl)quinazoline, which further nucleophilic substitution reaction with hydrazine hydrate afforded 4-hydrazinyl-6-(trifluoromethyl)-quinazoline. Finally, cyclocondensation of this intermediate with various substituted aromatic carboxylic acids led to the formation of the target triazolo[4,3-c]quinazoline derivatives (8a-h). The synthesised pyrimido[1,2-c]quinazolin-4-one and triazolo[4,3-c]quinazoline derivatives were evaluated for their anticancer potential against four human cancer cell lines, including HeLa (cervical cancer), COLO 205 (colon cancer), HepG2 (liver cancer) and MCF-7 (breast cancer). Biological evaluation revealed that compounds 5a and 5c displayed significant anticancer activity compared with the other derivatives. The molecular docking studies were also performed to explore the binding interactions of the most active compounds with the selected biological target and to support the observed experimental results.

Keywords

Trifluoromethyl group Triazole derivatives Anticancer activity Molecular docking interactions
(1)
Perumandla, R.; Gummula, S.; Kotte, S.; Betala, S. Synthesis of Novel Pyrimido[1,2-c]quinazolin-4-One and Triazolo[4,3-c]quinazoline Derivatives: Anticancer Activity and Docking Interactions. ajc 2026, 38, 1751-1758.
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