Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

Abstract

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 OPEN ACCESSMolecules 2014, 19 6652 the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

Breaking and Making of Rings: A Method for the Preparation of 4‐Quinolone‐3‐carb­oxylic Acid Amides and the Expensive Drug Ivacaftor

“…[13] Encouragingly, the addition of an external base [e.g., Et 3 N, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)] resulted in desired 4-quinolone-3-carboxylic acid amide 3 along with compound 2 (Scheme 2, Entries 2-4), which is in agreement with literature data. [14] On doubling the amount of base (Scheme 2, Entry 5), the desired product ratio was increased. To our delight, ozonolysis in a mixture of CH 2 Cl 2 /MeOH (5:1) under similar conditions improved the yield (58 %; Scheme 2, Entry 7).…”

Novas isoflavonas isoladas das folhas de <i>Vatairea guianensis</i> Aubl. e atividade antiprolifetariva

“…Após incubação à temperatura ambiente por 1 hora e centrifugação o sobrenadante foi removido, e a hemoglobina liberada foi medida espectrofotometricamente a 540 nm. DMSO era usado como controle negativo, e Triton X-100 (1%) foi usado como controle positivo [13].…”

“…O metabólito S1, apresentou-se como um sólido amarelo claro e solúvel em piridina, sua estrutura foi determinada com base na análise dos espectros de RMN 1 H, 13 De acordo com o espectro de RMN 13 C da substância S1, foi observado a presença de 21 carbonos, valor este igual ao número de carbono presente na estrutura, dentre eles seis carbonos metínicos (CH), três metílicos (CH3) e onze não hidrogenados. O sinal mais desblindado em 181,5 ppm atribuído ao carbono carbonílico (C-4), os sinais em δC 161,3 (C-7), 160,1 (C-5), 155,8 (C-9), 149,2 (C-4') e 148,4 (C-3') foram atribuídos aos cinco átomos de carbono aromáticos oxigenados (Figura 4).…”

“…A reunião de todos os dados discutidos levou à determinação da estrutura de S1, como um novo produto natural que recebeu o nome de Vatairenona A (Figura 9). O metabólito S2, apresentou-se como um sólido amorfo marrom e solúvel em metanol, sua estrutura foi determinada com base na análise dos espectros de RMN 1 H, 13 C, 2D e massa de alta resolução (HRESITOF-MS). Conforme o assinalamento segue abaixo: ✓ Um conjunto de sinais no RMN de 1 H na região de hidrogênios alifáticos, sendo dois singletos em δH 1,26 e 1,28 relacionados à duas metilas.…”

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

“…Even though the antibacterial profile has been the most common bioactivity associated with this class of substances [1], other types of pharmacological activities have also been explored and were successfully described by researchers around the world [3–4], such as antiviral [5–6], antiplasmoidal [7–8], anticancer [9–10], and trypanocide [11] activities. 4-Oxoquinoline-3-carboxamide derivatives, more specifically, have shown to be a promising structural scaffold for pharmacological profiles [12–22]. For example, Pasquini and co-workers have studied the application of N -adamantyl-4-oxoquinoline-3-carboxamide derivative 1 as selective cannabinoid type 2 receptor ligand with agonistic effect for analgesic response [13].…”