1609171-99-4Relevant academic research and scientific papers
Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors
Li, Jing,Jiang, Xiangyi,Dick, Alexej,Prakash Sharma, Prem,Chen, Chin-Ho,Rathi, Brijesh,Kang, Dongwei,Wang, Zhao,Ji, Xiangkai,Lee, Kuo-Hsiung,Cocklin, Simon,Liu, Xinyong,Zhan, Peng
, (2021/09/28)
The HIV-1 Capsid (CA) is considered as a promising target for the development of potent antiviral drugs, due to its multiple roles during the viral life cycle. Herein, we report the design, synthesis, and antiviral activity evaluation of series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors. Among them, 4-methoxy-N-methylaniline substituted phenylalanine (II-13c) and indolin-5-amine substituted phenylalanine (V-25i) displayed exceptional anti-HIV-1 activity with the EC50 value of 5.14 and 2.57 μM respectively, which is slightly weaker than that of lead compound PF-74 (EC50 = 0.42 μM). Besides, surface plasmon resonance (SPR) binding assay demonstrated II-13c and V-25i prefer to combine with CA hexamer rather than monomer, which is similar to PF-74. Subsequently, molecular dynamics simulation (MD) revealed potential interactions between representative compounds with HIV-1 CA hexamer. Overall, this work laid a solid foundation for further structural optimization to discover novel promising HIV-1 CA inhibitors.
Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells
Lee, Hsueh-Yun,Tsai, An-Chi,Chen, Mei-Chuan,Shen, Po-Jung,Cheng, Yun-Ching,Kuo, Ching-Chuan,Pan, Shiow-Lin,Liu, Yi-Min,Liu, Jin-Fen,Yeh, Teng-Kuang,Wang, Jing-Chi,Chang, Chi-Yen,Chang, Jang-Yang,Liou, Jing-Ping
, p. 4009 - 4022 (2014/06/09)
A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N- hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that 12 functions as a potent HDAC inhibitor with an IC50 value of 0.1 μM. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. It has a good pharmacokinetic profile with oral bioavailability of 33%. In in vivo efficacy evaluations in colorectal HCT116 xenografts, compound 12 suppresses tumor growth more effectively than SAHA (1, N-hydroxy-N′- phenyloctanediamide) and is therefore seen as a suitable candidate for further investigation.
