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Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

ABSTRACT: Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 ?M and 11.38 ?M, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1?/? kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 ?M). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 ?M).

SUBMITTER: Nascimento da Cruz AC

PROVIDER: S-EPMC6958387 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

Nascimento da Cruz Anne Cecília AC Brondani Dalci José DJ I Talo de Santana Temístocles T Oliveira da Silva Lucas L da Oliveira Borba Elizabeth Fernanda EF de Faria Antônio Rodolfo AR Ferreira Cavalcanti de Albuquerque Julianna J Piessard Sylvie S Matos Ximenes Rafael R Baratte Blandine B Bach Stéphane S Ruchaud Sandrine S Bezerra Mendonça Junior Francisco Jaime FJ Bazin Marc-Antoine MA Montenegro Rabello Marcelo M Hernandes Marcelo Zaldini MZ Marchand Pascal P Gonçalves da Silva Teresinha T

Pharmaceuticals (Basel, Switzerland) 20191117 4

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c in ...[more]

PMID: 31744203

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Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

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Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

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