Bioorganic Chemistry (2020)
Update date:2022-08-10
Topics:
Ahadi, Hamideh
Shokrzadeh, Mohammad
Hosseini-khah, Zahra
Ghassemi barghi, Nasrin
Ghasemian, Majid
Emadi, Elnaz
Zargari, Mehryar
Razzaghi-Asl, Nima
Emami, Saeed
The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26–3.90 μM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 μM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.
View MoreChongqing maohuan Chemicals Co., Ltd
website:http://www.bschem.com
Contact:+86 13996103726
Address:Chongqing Nan'an District Tu Town
Yicheng Goto Pharmaceuticals Co.,Ltd.
Contact:+86 710 3423122
Address:5th Floor,East Gate of Building #2,Servo-Industrial Park,1st Qilin Road,Xiangyang,Hubei,China
Contact:Tel:+86-29-88764861 Fax:+86-29-88764861
Address:Rm#2107, Block A, Epin Meidao Building, Gaoxin Rd, Hi-Tech Zone, Xi’an, China
Xiamen Hisunny Chemical Co.,Ltd
website:http://www.hisunnychem.com
Contact:+86-592-3327115
Address:Unit 603,No.879,Xiahe Road,Meixin Building,Xiamen,China
SHAANXI FUJIE PHARMACEUTICAL CO.,LTD
website:http://www.fujiepharm.com
Contact:+86-29-63650906
Address:Yuanqu Yi Road, Qinghe Food Industrial Park, Sanyuan County, Shaanxi Province, China
Doi:10.1016/S0031-9422(00)84014-5
(1983)Doi:10.1016/S0040-4020(01)97758-0
(1971)Doi:10.1002/chem.202003496
(2020)Doi:10.1149/1.2804422
(2008)Doi:10.1007/s11172-019-2557-5
(2019)Doi:10.1016/j.tetlet.2019.151120
(2019)