Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

Abstract

The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells) cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%), which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%). All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer). The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC 50 = 43-76 µM) and low cytotoxicity against Vero cells (IC 50 > 100 µM). The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity.Uniterms: Thiosemicarbazones/synthesis. Thiosemicarbazones/cytotoxic activity. Thiazoles/derivatives/ synthesis. Thiazoles/derivatives/cytotoxic activity. O estudo teve como objetivo a síntese de uma série de tiossemicarbazonas e seus derivados tiazólicos e a avaliação da atividade citotóxica contra três linhagens de células tumorais humanas e células normais (Vero), a fim de se avaliar o potencial pró-apoptótico dos compostos mais ativos. As tiossemicarbazonas foram obtidas por reação entre um aldeído aromático e tiossemicarbazida (rend. 71-96%), as quais foram submetidas à ciclização com α-bromoacetofenona, fornecendo os heterociclos tiazólicos desejados (rend. 63-100%). Todos os compostos sintetizados foram testados na concentração de 50 µM contra três linhagens de células tumorais: HL60 (leucemia promielocítica), Jurkat (leucemia linfoblástica aguda) e MCF-7 (câncer de mama). O efeito pró-apoptótico foi avaliado por citometria de fluxo como porcentagem de células com DNA hipodiplóide. Três compostos tiazólicos foram ativos contra, pelo menos, uma linhagem tumoral (CI 50 =43-76 µM), com baixa citotoxicidade contra células Vero (CI 50 > 100 µM). O composto mais ativo dessa série induziu fragmentação do DNA de 91% e 51% nas linhagens HL60 e MCF-7, respectivamente, sugerindo que este composto ativou a apoptose nessas células. Dentre os compostos sintetizados, um em particular apresentou atividade antiproliferativa e pró-apoptótica em células tumorais e pode ser considerado composto protótipo promissor na busca por novos análogos com atividade melhorada.

4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile

“…From result of structure activity relationship study, we may conclude that different structural requirements are required for a molecule to be effective against different goal. The aforementioned facts are supported by the earlier research findings [8, 24, 25].…”

Thiazole Ring—A Biologically Active Scaffold

“…Braga et al [96] synthesized a series of thiazole derivatives with the purpose to investigate their cytotoxicity against three human cancer cell lines: HL-60 (promyelotic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer) as well as normal (Vero cells) cell lines. Compounds were tested in vitro at a concentration of 50 µM, while the reference drug etoposide was investigated at 10 µM.…”

Synthesis and Biological Screening of New 2-(5-Aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl Thiazole Derivatives as Potential Antimicrobial Agents

“…Representative examples of thiazole-containing marketed drugs are showcased in Figure . Its derivatives have a wide range of biological activities such as antimicrobial, antituberculosis, anticancer, antiviral, antidiabetic, antimalarial, antitrypanosomal, anti-inflammatory, analgesic, antioxidant, and anticonvulsant …”