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Eur J Med Chem ; 226: 113864, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626877


Pathogenic bacteria use an intercellular chemical communication system called quorum sensing (QS) to control the expression of cellular functions such as virulence factors, biofilm formation, toxin production, and antibiotic resistance in a manner that is highly dependent on population density. Hence, since the emergence of QS, there has been a great interest in exploiting the QS mechanism as a new drug target. Therefore, blocking the QS mechanism can be an effective strategy to control infection and solve the problem of drug resistance. So far, there is no clinically approved anti-QS drug that can disable the circuits of QS systems. This review discusses the quorum-sensing network systems and novel anti-QS inhibitors in some Gram-negative bacteria.

Anticancer Agents Med Chem ; 21(7): 811-824, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32329698


BACKGROUND: Isoquinoline analogs are an important, structurally diverse class of compounds that are extensively used as pharmaceuticals. Derivatives containing the isoquinoline scaffold have become a focus of therapeutic research because of their wide range of biological characteristics. Examples of these drugs, many of which are in clinical application or at the pre-clinical stage, are used to treat a broad swathe of ailments, such as tumors, respiratory diseases, infections, nervous system diseases, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases. METHODS: Data were collected from PubMed, Web of Science, and SciFinder, through searches of drug names. RESULTS: At least 38 isoquinoline-based therapeutic drugs are in clinical application or clinical trials, and their chemical structure and pharmacokinetics are described in detail. CONCLUSION: The isoquinoline ring is a privileged scaffold which is often preferred as a structural basis for drug design, and plays an important role in drug discovery. This review provides a guide for pharmacologists to find effective preclinical/clinical drugs and examines recent progress in the application of the isoquinoline scaffold.

Eur J Med Chem ; 161: 493-505, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388465


To explore anti-gastric cancer agents with high efficacy and selectivity, we report the design, synthesis and optimization of a novel series of 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives starting from the compound PCA-15 reported by us previously. Most of the target compounds demonstrated significant antiproliferative effects on MGC803 cancer cell line, and more potent than the positive control (PCA-15 and 5-Fu). Among them, compound 6o was identified to be the most active compound against MGC803 cell line with an IC50 value of 0.84 µM. Additionally, high selectivity was also observed between cancer and normal cells (23.35 µM against GES-1). Further mechanism studies confirmed that compound 6o could inhibit colony formation and migration, induce the apoptosis of MGC803 cells through both the mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which were evidenced by the up-regulation of Bax, cleaved-caspase 9/3/8, cleaved PARP and down-regulation of Bcl-2. Our systematic studies implied a new scaffold targeting gastric cancer cells for further development of small-molecule compounds with improved potency and selectivity.

Antineoplásicos/farmacologia , Chalconas/farmacologia , Desenho de Fármacos , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/síntese química , Chalconas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade
Eur J Med Chem ; 143: 1396-1405, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29113745


Pteridines are an important class of heterocyclic compounds with diverse biological activities. Here, we report a series of pteridin-7(8H)-one derivatives and their antiproliferative activities toward MKN-45, MGC-803, EC-109, and H1650. Structure-activity relationship studies showed that compound 12 exerted the most potent antiproliferative activity against MKN-45 and MGC-803 with the IC50 values of 4.32 and 7.01 µM, respectively. Besides, compound 12 induced morphological changes and apoptosis of MKN-45 cells, increased expression of Bax, down-regulated expression of Bcl-2 and caused cleavage of caspase-3/9. Additionally, we first reported the construction of the novel bicyclic 8,9-dihydro-7H-purine-8-carboxylate scaffold through the competitive 5-endo cyclization reaction with two C-N bonds and a chiral carbon center established.

Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pteridinas/síntese química , Pteridinas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Pteridinas/química , Relação Estrutura-Atividade