Synthesis of Some Novel Thiazole, Thiadiazole and 1,4-Phenylene-bis-thiazole Derivatives as Potent Antitumor Agents

Abstract

A novel series of 2-ethylidenehydrazono-5-arylazothiazoles 5a-h and 2-ethylidenehydrazono-5-arylazothiazolones 9a-d were prepared by cyclocondensation of hydrazonyl halides 3a-h and 7a-d with ethylidenethiosemicarbazide 2. In addition, reaction of 2 with N-phenylcarbohydrazonyl chloride (14), afforded 1,3,4-thiadiazole derivative 17 as the end product. Moreover, the thiosemicarbazide derivative 2 was reacted with various bromoacetyl compounds 19a-d and 1,1'-(1,4-phenylene)bis(2-bromoethanone) (21) furnished the respective thiazole derivatives 20a-d and 1,4-phenylene-bisthiazole derivative 22. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. The newly synthesized compounds were evaluated for their antitumor activities against hepatocellular carcinoma (HepG2) cell line and the results revealed promising activities of compounds 5h, 5d, 5g, 5f and 5e with IC50 equal 2.23 ± 0.28, 2.48 ± 0.34, 2.49 ± 0.24, 4.03 ± 0.11, and 5.32 ± 0.27 μM, respectively. Functionalized thiazole derivatives have received much attention due to their diverse biological activities such as antimicrobial, 1 antiviral, 2 cytotoxic and antitumor, 3-6 and HIV-protease inhibitory agents. 7 Compounds incorporating two thiazole rings either directly connected as in bisthiazoles or through a linker unit as in bisthiazolyl compounds, show pronounced biological activity as DNA replication inhibitors in the tumor cells 8 and HIV-protease inhibitors. 7-9 Pyridine deivatives also play a key role catalyzing both biological and chemical systems. In many enzymes of living organisms it is the prosthetic pyridine nucleotide (NADP) that is involved in various 954

Utility of Pyrazolylchalcone Synthon to Synthesize Azolopyrimidines under Grindstone Technology

“…[15][16][17][18][19][20] In continuation of our previous work to discover new bioactive heterocyclic compounds, [21][22][23][24][25][26][27][28][29][30][31] we aimed here to synthesize new pyrazolyl-azolopyrimidines via ecofriendly method to evaluate their antibacterial activity.…”

A Facile Three‐Component One‐Pot Synthesis of Some Novel Tricyclic Hetero‐Ring Systems

“…Compounds 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k and 2a , 2b , 2c , 2d , 2e (Fig. ) recently obtained in our laboratory seemed suitable candidates to fulfill our objective by virtue of their β‐diketone and the active methylene groups.…”

Synthesis and characterization of some novel bis‐thiazoles

“…[9][10][11][12][13][14][15] In this current work, we geared our research toward the synthesis of some new bis-thiazoles with highly expected bioactive potential. [16][17][18][19][20][21][22][23][24][25] Herein, we present the synthesis of some new bisthiazoles 6, 14, 16, 18, bis-thiazolines 9, 20, and bisthiadiazole 12 derivatives via the reaction of bisthiosemicarbazone derivative 3 with various hydrazonoyl halides 4, 7, 10, or α-haloketones 13, 15, 17, and 19.…”