Bioorganic Chemistry p. 386 - 392 (2019)
Update date:2022-08-05
Topics:
Thacker, Pavitra S.
Alvala, Mallika
Arifuddin, Mohammed
Angeli, Andrea
Supuran, Claudiu T.
A series of novel 7-hydroxycoumarin-3-carboxamides was synthesized by the reaction of 7-hydroxy-2-oxo-2H-chromene-3-carboxylic acid with various substituted aromatic amines. The newly synthesized compounds were evaluated for their inhibitory activity against the four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms CA I, CA II, CA IX and CA XII. The CA inhibition results show that the newly synthesized 7-hydroxycoumarin-3-carboxamides (4a-n) exhibited selective inhibition of the tumor associated isoforms, CA IX and CA XII over CA I and II isoforms. The inhibition constants ranged from sub micromolar to low micromolar. Amongst all the compounds tested, compound 4m was the most effective inhibitor exhibiting sub micromolar potency against both hCA IX and hCA XII, with a Ki of 0.2 μM. Therefore, it can be anticipated that compound 4m can serve as a lead for development of anticancer therapy by exhibiting a novel mechanism of action. The binding modes of the most potent compounds within hCA IX and XII catalytic clefts were investigated by docking studies.
View MoreJIANGXI ZHANGFENG CHEMICAL CO., LTD.
Contact:+86-0799-3413066
Address:Xiyuan village, Xiabu Town, Xiangdong District
Suzhou Kangrun Pharmaceutical, Inc
Contact:86-512-63912376,63913329
Address:Building 2, No. 2358 ,Chang'an Rd, Wujiang Economic Development Zone Pioneering park, china
Contact:+86-579-85206992
Address:No 451 chouzhou north road ,room 1106 int'l business center , yiwu ,china
Hebei Fulong Import & Export Co., Ltd.
Contact:86-311-87795661
Address:15A19 Zhongyuan Building,368 Youyi North Street,Shijiazhuang 050070,China
Ceresking Ecology & Technology co.,ltd
Contact:86 22 66218397
Address:Room 1613, Zheshang Mansion, No. 1988, Yingbin Avenue, Binhai New District, Tianjin,China.
Doi:10.1021/ol702291r
(2007)Doi:10.1021/ol301482f
(2012)Doi:10.1016/0022-328X(87)85091-X
(1987)Doi:10.1021/ol0362562
(2004)Doi:10.1021/jo00403a029
(1978)Doi:10.1021/jacs.7b01373
(2017)