Synthesis, docking and biological evaluation of some novel [1,2,4] triazolo [5,1-b] quinazoline Schiff base derivatives

• Published in: Journal of the Iranian Chemical Society 2024-04, Vol.21 (4), p.1055-1067
• Main Authors: Jowkar, Zahra, Aboonajmi, Jasem, Heiran, Roghayeh, Jarrahpour, Aliasghar, Sharghi, Hashem, Riazimontazer, Elham, Sinou, Véronique, Rouvier, Florent, Brunel, Jean-Michel
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Antiparasitic agents; Biochemistry; Biological activity; Chemistry; Chemistry and Materials Science; Dihydrofolate reductase; Docking; Imines; Inorganic Chemistry; Malaria; NMR; Nuclear magnetic resonance; Organic Chemistry; Physical Chemistry; Reductases; Stereoisomerism; Stereoselectivity; Synthesis
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-024-02975-2

In this work, a novel series of racemic Schiff bases bearing the biologically active [1,2,4]triazolo[5,1-b]quinazoline scaffold has been synthesized in good to excellent yields, and fully characterized by FTIR, 1 H NMR and 13 C NMR, as well as elemental analyses. The in vitro antimalarial activities of these derivatives have been evaluated against Plasmodium falciparum ( P. falciparum ) K1 strain and exhibited IC 50 values ranged from 15.4 to 44.4 µM. Among them, 4e, 4j, 4 l, and 4f lead to the best results with IC 50 of 15.4, 15.8, 16.8, and 17.3 µM, respectively. The observed activity was further substantiated by docking study on wild-type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS). According to docking results, (S) stereoisomer of these synthesized compounds has the best score among them. The (S) stereoisomer shows probably more stable binding with the active site of the enzyme and can be considered as a candidate for stereoselective synthesis and biological evaluation in future studies. Moreover, among four synthetic derivatives that showed prominent antimalarial activity (4e, 4j, 4 l and 4f), 4e has the minimum Gibbs binding energy, and it is consistent with the biological activity. The new compounds were also accomplished against both Gram-positive and Gram-negative bacteria, but no promising effect was observed, even at concentrations up to 400 µg/mL.