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

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Abstract

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, 1H NMR and 13C 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 IC50 values ranged from 15.4 to 44.4 µM. Among them, 4e, 4j, 4 l, and 4f lead to the best results with IC50 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.

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Acknowledgements

Funding for this research was generously provided by the Shiraz University Research Council (Grant No. 93-GR-SC-23).

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Authors and Affiliations

  1. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795, Iran

    Zahra Jowkar, Jasem Aboonajmi, Aliasghar Jarrahpour & Hashem Sharghi

  2. Estahban Higher Education Center-Shiraz University, Estahban, Iran

    Roghayeh Heiran

  3. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Elham Riazimontazer

  4. Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Elham Riazimontazer

  5. Aix Marseille Univ, INSERM, SSA, MCT, 13385, Marseille, France

    Véronique Sinou, Florent Rouvier & Jean-Michel Brunel

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  1. Zahra Jowkar
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Jowkar, Z., Aboonajmi, J., Heiran, R. et al. Synthesis, docking and biological evaluation of some novel [1,2,4] triazolo [5,1-b] quinazoline Schiff base derivatives. J IRAN CHEM SOC 21, 1055–1067 (2024). https://doi.org/10.1007/s13738-024-02975-2

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