Journal of Medicinal Chemistry p. 10860 - 10874 (2018)
Update date:2022-08-17
Topics:
Nocentini, Alessio
Trallori, Elena
Singh, Srishti
Lomelino, Carrie L.
Bartolucci, Gianluca
Di Cesare Mannelli, Lorenzo
Ghelardini, Carla
McKenna, Robert
Gratteri, Paola
Supuran, Claudiu T.
Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs.
View MoreChengdu Sino-Strong Pharmaceutical Co.,Ltd.
website:http://www.sino-strong.com.cn
Contact:+86-28-82666753
Address:459 West haike road,Cross-straits technological industry park, Wenjiang district,Chengdu, P.R.China
Wuhan Jadechem International Trade Co.,Ltd.
website:http://www.jadechem-intl.com
Contact:+86-27-83527060
Address:Room502,Building C11,Software new city No.9,Huacheng Avenue,East Lake High-tech development zone,Wuhan,Hubei,China
Jiangxi Dongxu Chemical Science & Technology Co.,Ltd
Contact:+86-791-86899381
Address:Nanchang, Jiangxi, China
Contact:0086-22-2822 1962 / 2822 1963
Address:B-808, No. 1, North-South Street, Hexi District,
Dezhou Longteng Chemical Co., Ltd.
website:http://www.sodium-methoxide.cn/
Contact:0086-18866052283
Address:Xinhua Industrial Zone, Dezhou City, Shandong Province, China
Doi:10.1080/10610278.2017.1371719
(2018)Doi:10.1021/acs.orglett.1c01921
(2021)Doi:10.1021/acs.orglett.5b01912
(2015)Doi:10.1039/c39720000780
(1972)Doi:10.1016/S0040-4039(00)74555-2
(1980)Doi:10.1248/cpb.c18-00546
(2018)