[1,2,4]triazolo[4,3-a]quinazolin-5-one deriva tives as antimalarial agents

S. Yu. Danylchenko, S. S. Kovalenko, O. G. Drushlyak, S. M. Kovalenko, L. Maes

Abstract


Five novel [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one derivatives containing an amide group connected to 1 position of triazoloquinazoline moiety via sulfur-carbon or carbon chain were synthesized. The structure was confirmed by elemental analysis and 1H NMR spectroscopy. Their in vitro antiprotozoal activity was evaluated against Leishmania infantum, Plasmodium falciparum, Trypanosoma brucei and Trypanosoma cruzi. 4-Benzyl-1-{4-[4-(4-methoxyphenyl)piperazin-1-yl]-4-oxobutyl}[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one 7e with an amide group connected via carbon chain showed noticeable antimalarial activity (IC50 0.2 µM). The lead structure 7 e may be promising for further investigations as novel antimalarial agents.

Keywords


2-hydrazinoquinazolin-4(3H)-ones; [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones; in vitro; antiprotozoal; antimalaria activity

References


Danilchenko S.Yu. / Synthesis of substituted 2-hydrazinoquinazolin-4-ones as intermediates for heterocyclic compounds synthesis // S.Yu. Danilchenko, O.G. Drushlyak, S.M. Kovalenko // Journal of Organic and Pharmaceutical Chemistry. – 2014. – Vol. 12(3). P. 66-73.

Abdel Gawad N.M. Design, synthesis, and anticonvulsant activity of novel quinazolinone analogues / N.M. Abdel Gawad, H.H. Georgey, R.M. Youssef et al. // Medicinal Chemistry Research. – 2011. – Vol. 20. – P. 1280–1286.

Alagarsamy V. AntiHIV, antibacterial and antifungal activities of some novel 1,4-disubstituted-1,2,4-triazolo[4,3-a] quinazolin-5(4H)-ones / V. Alagarsamy, R. Giridhar, M.R. Yadav et al. // Indian Journal of Pharmaceutical Sciences. – 2006. – Vol. 68, Issue 4. – P. 532–535.

Alagarsamy V. 4-(3-Methoxyphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones: new class of H1-antihistaminic agents / V. Alagarsamy, H.K. Sharma, P. Parthiban et al. // Pharmazie. – 2009. – Vol. 64. – P. 5–9.

Alagarsamy V. Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as a new class of H1-antihistaminic agents / V. Alagarsamy, K. Kavitha, M. Rupeshkumar et al. // Acta Pharmaceutica. – 2009. – Vol. 59. – P. 97–106.

Alagarsamy V. Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents / V. Alagarsamy, M. Rupeshkumar, K. Kavitha et al. // European Journal of Medicinal Chemistry. – 2008. – Vol. 43, Issue 11. – P. 2331–2337.

Alagarsamy V. Synthesis of 4-butyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents / V. Alagarsamy, D. Shankar, S. Murugesan // Biomedicine & Pharmacotherapy. – 2008. – Vol. 62, Issue 3. – P. 173–178.

Buckner F.S. Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase / F.S. Buckner, C.L. Verlinde, A.C. La Flamme et al. // Antimicrobial Agents and Chemotherapy. – 1996. – Vol. 40. – P. 2592–2597.

Cos P. Anti-infective potential of natural products: How to develop a stronger in vitro proof-of-concept / P. Cos, A.J. Vlietinck, D.V. Berghe et al. // The Journal of Ethnopharmacology. – 2006. – Vol. 106. – P. 290–302.

Deshmukh M.B. Synthesis and antimicrobial screening of pyrazolo-3-aryl quinazolin-4(3H)ones / M.B. Deshmukh, S. Patil, S.S. Patil et al. // Indian Journal of Pharmaceutical Sciences. – 2010. – Vol. 72(4). – P. 500–504.

Elansary A.K. Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma / A.K. Elansary, H.H. Kadry, E.M. Ahmed et al. // Medicinal Chemistry Research. – 2012. – Vol. 21. – P. 3327–3335.

Gaudilliere B. Nouvelles 1-aminotriazolo[4,3-a]quinazoline-5-ones inhibitrices de phosphodiesterases IV / B. Gaudilliere, R. Lavalette, C. Andrianjara // Patent France 2792938, (2000).

Gobinath M. Anticancer and antitubercular study of some 1,4-disubstituted[1,2,4]-triazolo[4,3-a]quinazolin-5(4H)-ones / M. Gobinath, N. Subramanian, V. Alagarsamy // International Journal of Research in Pharmaceutical Sciences. – 2012. – Vol. 3 (1). – P. 146-149.

Gobinath M. Design, synthesis and H1-antihistaminic activity of novel 1-substituted-4-(3-chlorophenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones / M. Gobinatha, N. Subramanianb, V. Alagarsamy // Journal of Saudi Chemical Society. – 2015. –Vol. 19, № 3. – Р. 282–286.

Gobinath M. Synthesis of 1-substituted-4-(pyridin-4-yl)[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones as a new class of H1-antihistaminic agents / M. Gobinath, N. Subramanian, V. Alagarsamy et al. // Tropical Journal of Pharmaceutical Research. – 2015. – Vol. 14, Issue 2. – P. 271–277.

Hirumi H. Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers / H. Hirumi, K. Hirumi // The Journal of Parasitology. – 1989. – Vol. 75. – P. 985–989.

Makler M.T. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity / M.T. Makler, J.M. Ries, J.A. Williams et al. // The American Journal of Tropical Medicine and Hygiene. – 1993. – Vol. 48. – P. 739–741.

Raz B. The Alamar Blue asssay to determine drug sensitivity of African trypanosomes (T. b. rhodesiense, T. b. gambiense) in vitro / B. Raz, M. Iten, Y. Grether-Buhler et al. // Acta Tropica. – 1997. – Vol. 68. – P. 2592–2597.


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DOI: https://doi.org/10.24959/89561

Abbreviated key title: Ukr. bìofarm. ž.

ISSN 2519-8750 (Online), ISSN 2311-715X (Print)