87165-11-5Relevant academic research and scientific papers
Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer
Endo, Satoshi,Oguri, Hiroaki,Segawa, Jin,Kawai, Mina,Hu, Dawei,Xia, Shuang,Okada, Takuya,Irie, Katsumasa,Fujii, Shinya,Gouda, Hiroaki,Iguchi, Kazuhiro,Matsukawa, Takuo,Fujimoto, Naohiro,Nakayama, Toshiyuki,Toyooka, Naoki,Matsunaga, Toshiyuki,Ikari, Akira
, p. 10396 - 10411 (2020)
Aldo-keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, N-(4-fluorophenyl)-8-hydroxy-2-imino-2H-chromene-3-carboxamide (2d), and synthesized its derivatives with IC50 values of 25-56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).
Synthesis, anticancer activity and radiosensitizing evaluation of some new 2-pyridone derivatives
El-Said,El-Gazzar,Al-Dosari,Ghorab
, p. 149 - 156 (2012)
Based on the reported anticancer activity of 2-pyridone, a new series of 6-amino-5-cyano-1-(3-ethylphenyl)-2-oxo-4-substituted-1,2-dihydropyridine-3- carbo-nitriles 4a-p were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line and liver human tumor cell line (HEPG2). Radiosensitizing activity was also evaluated. The starting material 2-cyano-N-(3-ethylphenyl)-acetamide 3 was obtained via reaction of 3-ethyl aniline 1 with ethyl cyanoacetate under condition of fusion. Upon treatment of compound 3 with aromatic aldehyde and malononitrile in the presence of catalytic amount of piperidine yielded the corresponding 1,2-dihydropyridine derivative 4a-p. Also chromenes 5 and 6 were obtained in good yield via reaction of compound 3 with salicyladehyde under different condition. The chromene derivatives 5 and 6 were further reacted with malononitrile in NH 4OAc, afford the corresponding chromenopyridones 7 and 8. The structures of the synthesized compounds 3-8 were confirmed by analytical and spectral data. Compounds 4d, 4e, 5 and 6 showed higher anticancer activity against EAC cell line with IC50 values (75.32, 20.77, 73.1 and 67.05 M) compared to doxorubicin as positive control with IC50 value (68.13 M), moreover, these compounds showed potent activity on HEPG2 cell line with IC50 values (26.5, 19.2, 39.3, 44.9 M), respectively, compared to doxorubicin (CAS 29042-30-6) (38.46 M) and their activity increased synergistically when combined with γ-radiation. Georg Thieme Verlag KG Stuttgart · New York.
Synthesis, antibacterial and cytotoxic activities of cyanoenonebenzenesulfonamide, acetamide and pyridine-3-Carbonitrile derivatives
Alsaid, Mansour S.,Ghorab, Mostafa M.,Kuete, Victor,Shahat, Abdelaaty A.,Efferth, Thomas
, p. 8505 - 8510 (2015/02/02)
A series of sulfonamides having biologically active acrylamides moieties (2, 3, 5), penta-2,4-dienamide (4), chromene-2-carboxamide (6), acetamide derivatives (7, 8) and pyridone derivative (9) were prepared. The structure of the synthesized compounds was
