New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity

0508040 - MBÚ 2020 RIV FR eng J - Journal Article
Fernanda Castano, L. - Cuartas, V. - Bernal, A. - Insuasty, A. - Guzman, J. - Vidal, O. - Rubio, V. - Puerto, G. - Lukáč, Pavol - Vimberg, Vladimír - Balíková Novotná, Gabriela - Vannucci, Luca - Janata, Jiří - Quiroga, J. - Abonia, R. - Nogueras, M. - Cobo, J. - Insuasty, B.
New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity.
European Journal of Medicinal Chemistry. Roč. 176, AUG 15 (2019), s. 50-60. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MŠMT(CZ) EF16_027/0007990
Institutional support: RVO:61388971
Keywords : Antibacterial * Anticancer * Antituberculosis
OECD category: Microbiology
Impact factor: 5.573, year: 2019
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0223523419304222?via%3Dihub

New sulfonamides 5/6 derived from 4-methoxyacetophenone I were synthesized by N-sulfonation reaction of ammonia (3) and aminopyrimidinone (4) with its sulfonyl chloride derivative 2. Sulfonamides 5 and 6 were used as precursors of two new series of chalcones 8a-f and 9a-f, which were obtained through Claisen-Schmidt condensation with aromatic aldehydes 7a-f. Compounds 5/6, 8a-d, 8f, 9a-d, and 9f were screened by the US National Cancer Institute (NCI) at 10 mu M against sixty different human cancer cell lines (one-dose trial). Chalcones 8b and 9b satisfied the pre-determined threshold inhibition criteria and were selected for screening at five different concentrations (100, 10, 1.0, 0.1, and 0.01 mu M). Compound 8b exhibited remarkable GI(50) values ranging from 0.57 to 12.4 mu M, with cytotoxic effects being observed in almost all cases, especially against the cell lines K-562 of Leukemia and LOX IMVI of Melanoma with Gl(50) = 0.57 and 1.28 mu M, respectively. Moreover, all compounds were screened against Mycobacterium tuberculosis H37Rv, chalcones 8a-c and 9a-c were the most active showing MIC values between 14 and 42 mu M, and interestingly they were devoid of antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus. These antituberculosis hits showed however low selectivity, being equally inhibitory to M. tuberculosis and mammalian T3T cells. The chalcone-sulfonamide hybrids 8a-f and 9a-f resulted to be appealing cytotoxic agents with significant antituberculosis activity. (C) 2019 Elsevier Masson SAS. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0298995