914658-49-4Relevant articles and documents
Design, synthesis, in vitro and in silico studies of novel 4-oxoquinoline ribonucleoside derivatives as HIV-1 reverse transcriptase inhibitors
Forezi, Luana da S.M.,Ribeiro, Mariana M.J.,Marttorelli, Andressa,Abrantes, Juliana L.,Rodrigues, Carlos R.,Castro, Helena Carla,Souza, Thiago Moreno L.,Boechat, Fernanda da C.S.,de Souza, Alessandra M.T.,de Souza, Maria Cecília B.V.
, (2020/04/02)
Human immunodeficiency virus type 1 (HIV-1) is a public health problem that affects over 38 million people worldwide. Although there are highly active antiretroviral therapies, emergence of antiviral resistant strains is a problem which leads to almost a million death annually. Thus, the development of new drugs is necessary. The viral enzyme reverse transcriptase (RT) represents a validated therapeutic target. Because the oxoquinolinic scaffold has substantial biological activities, including antiretroviral, a new series of 4-oxoquinoline ribonucleoside derivatives obtained by molecular hybridization were studied here. All synthesized compounds were tested against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), and 9a and 9d displayed the highest antiviral activities, with IC50 values of 1.4 and 1.6 μM, respectively. These compounds were less cytotoxic than AZT and showed CC50 values of 1486 and 1394 μM, respectively. Molecular docking studies showed that the most active compounds bound to the allosteric site of the enzyme, suggesting a low susceptibility to the development of antiviral resistance. In silico pharmacokinetic and toxicological evaluations reinforced the potential of the active compounds as anti-HIV candidates for further exploration. Overall, this work showed that compounds 9a and 9d are promising scaffold for future anti-HIV-1 RT drug design.
Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3- carboxamide derivatives: Finding new potential anticancer drugs
Forezi, Luana Da S. M.,Tolentino, Nathalia M. C.,De Souza, Alessandra M. T.,Castro, Helena C.,Montenegro, Raquel C.,Dantas, Rafael F.,Oliveira, Maria E. I. M.,Silva Jr., Floriano P.,Barreto, Leilane H.,Burbano, Rommel M. R.,Abrahim-Vieira, Barbara,De Oliveira, Riethe,Ferreira, Vitor F.,Cunha, Anna C.,Boechat, Fernanda Da C. S.,De Souza, Maria Cecilia B. V.
, p. 6651 - 6670 (2014/06/10)
As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10-18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.
