332110-07-3Relevant articles and documents
Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents
Ahadi, Hamideh,Shokrzadeh, Mohammad,Hosseini-khah, Zahra,Ghassemi barghi, Nasrin,Ghasemian, Majid,Emadi, Elnaz,Zargari, Mehryar,Razzaghi-Asl, Nima,Emami, Saeed
, (2020/11/03)
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.
Design, synthesis, and biological evaluation of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives as anticancer agents
Aghcheli, Ayoub,Toolabi, Mahsa,Ayati, Adileh,Moghimi, Setareh,Firoozpour, Loghman,Bakhshaiesh, Tayebeh Oghabi,Nazeri, Elahe,Norouzbahari, Maryam,Esmaeili, Rezvan,Foroumadi, Alireza
, p. 2000 - 2010 (2020/08/26)
A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells (IC50 = 0.37, 0.73 and 0.95 μM, respectively) which were significantly more potent than sorafenib as the reference drug (IC50 = 7.91 μM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2.
Ultrasound-assisted improved synthesis of 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives: an experimental and computational study
Erdogan, Taner
, p. 899 - 912 (2019/04/08)
The main objects of this study are: (1) to propose alternative efficient methods for the synthesis of 5-amino-1,3,4-thiadiazole-2-thiol and 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives, (2) to investigate the reactions and the chemical species which take place in the investigated reactions computationally via density functional theory (DFT) calculations, (3) to make a comparison between experimental and computationally obtained data, and (4) to make a comparison between the computational methods to find out the best computational technique to simulate the investigated molecules and reactions. The study consists of two parts. In the first part, synthesis of 5-amino-1,3,4-thiadiazole-2-thiol and 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives have been carried out. For both syntheses, it has been proposed that the reactions can be carried out effectively with the use of ultrasound. To the best of our knowledge, this is the first use of ultrasound for both reactions. The results showed that ultrasound can increase the efficiency of the investigated reactions and can be a good alternative to conventional methods. In the second part of the study, some DFT calculations have been performed on the chemical species which take place in the investigated reactions. In computational studies, seven different basis sets have been used. In this second part, comparisons have been made (1) between experimental and computationally obtained data, and (2) between the computational techniques to reveal the best method for the investigated molecules.
Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease
Liu, Hailong,Wu, Ruoming,Sun, Yanyan,Ye, Yan,Chen, Jing,Luo, Xiaomin,Shen, Xu,Liu, Hong
, p. 6344 - 6352 (2014/12/11)
Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 μM based on in vitro DENV2 NS2B-NS3pro assays.
Synthesis and in vitro biological evaluation of farnesylthiosalicylic acid derivatives as anti-tumor carcinoma agents
Ling, Yong,Chen, Guang Tong,Wang, Dong Geng,Li, Yu Qin,Wang, Xin Yang,Xiao, You An,Zheng, Heng
, p. 1141 - 1144,4 (2020/07/31)
Novel farnesylthiosalicylic acid (FTA) derivatives 5a-m with different substituted 1,3,4-thiadiazoles were synthesized. Compounds 5b, 5c, 5e and 5f displayed anti-tumor activities superior to FTA in most cancer cells tested. Furthermore, 5e induced tumor cell apoptosis, which was accompanied by lower Bcl-2 expression, but with higher Bax and caspase 3 expression activities in cancer cells.
Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents
Radi, Marco,Crespan, Emmanuele,Botta, Giorgia,Falchi, Federico,Maga, Giovanni,Manetti, Fabrizio,Corradi, Valentina,Mancini, Manuela,Santucci, Maria Alessandra,Schenone, Silvia,Botta, Maurizio
, p. 1207 - 1211 (2008/09/20)
A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has been discovered as potent Abl tyrosine kinase inhibitors. Molecular docking simulations on the Abl tyrosine kinase were conducted in order to rationalize the SAR of the synthesized inhibitors. The most active compound identified from the enzymatic screening (6a) showed interesting inhibitory activity on Imatinib-sensitive murine myeloid 3B clone and Bcr-Abl-independent Imatinib-resistant leukemia cells. Surprisingly, 6a was also proved to act as differentiating inducers in human promyelocytic leukemia cells (HL-60).
