RESUMEN
Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.
Asunto(s)
Alcaloides/química , Antineoplásicos/farmacología , Carbazoles/química , Alcaloides/farmacología , Antineoplásicos/química , Carbazoles/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , HumanosRESUMEN
BACKGROUND: Androgen receptor is an attractive target for the treatment of prostate cancer. The 1,3- thiazolidine-2,4-diones possess a wide diversity of important biochemical effects and interesting pharmacological properties. OBJECTIVE: The aim of the study is to find the experimental and computational methods to investigate the interference of 1,3-thiazolidine-2,4-diones with androgen receptor against prostate cancer. METHOD: Structural modification and molecular docking-based virtual screening approaches were imposed to identify the novel 1,3-thiazolidine-2,4-diones by using Schrödinger (Maestro 9.5). The best fit molecules (3-12 & 23-31) were synthesized and characterized using spectroscopic techniques, then in vitro antioxidant and antiprostate cancer activities were evaluated. Further, the structure of the intermediate (18) was confirmed by single crystal XRD analysis. The mechanism studies were performed through the gene expression for the compounds, 29, 30, and 31, the standards, dihydrotestosterone and R-bicalutamide. RESULTS: The compounds, 29, 30 and 31 showed comparatively significant antioxidant activity and better antiproliferative activity against PC-3 and LNCaP cell lines. Also, very low cytotoxicity was observed in the noncancerous cell (3T3). The compounds, 29, 30 and 31 significantly decreased the mRNA expression of ARstimulated genes, PSA and TMPRSS2, which demonstrated their anti-prostate cancer activities. ADME/T properties prediction of the compounds (3-12 and23-31) showed the promising drug-likeness and pharmacokinetic parameters without toxicity. Moreover, DFT calculations apparently confirmed the stable conformer of the compound, 31. CONCLUSION: These findings may provide the essential information for the development of anti-prostate cancer agents.