- Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide–hydrazone and carboxamide moiety
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A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide–hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50values of 2.21?μg/mL, 1.67?μg/mL and 1.11?μg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide–hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.
- He, Haifeng,Wang, Xiaoyan,Shi, Liqiao,Yin, Wenyan,Yang, Ziwen,He, Hongwu,Liang, Ying
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- Design, Synthesis, and Insecticidal Activity of Novel Doramectin Derivatives Containing Acylurea and Acylthiourea Based on Hydrogen Bonding
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Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds (5o, 5t, and 6t) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound 3g in our laboratory. Specifically, compound 5t was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC50 value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC50 value of 40.5507 mg/L), and 3.98-fold higher potency than compound 3g (LC50 value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound 5t (2.17, 2.20, 2.56, and 2.83 ?) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound 5o (1.64 and 2.15 ?) and compound 6t (2.20 and 2.31 ?) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.
- Bai, Ping,Cheng, Yao,Lu, Xiaoxia,Yang, Jian,Zhang, Qi,Zheng, Cheng
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p. 5806 - 5815
(2020/06/19)
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- Convenient One-Pot Two-Step Synthesis of Symmetrical and Unsymmetrical Diacyl Ureas, Acyl Urea/Carbamate/Thiocarbamate Derivatives, and Related Compounds
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A wide range of chemicals such as amides, hydrazides, amines, alcohols, carbazate, and sulfonate were reacted with acyl isocyanates generated by the reaction of primary amides with oxalyl chloride to give symmetrical and unsymmetrical diacyl urea derivatives, acyl ureas/carbamates/thiocarbamates, and related compounds. This method provides means for convenient one-pot, two-step synthesis of compounds bearing urea, carbamate, and other functional groups from cheap and commercially available starting reagents. It is expected that the results presented in this report will expand the medicinal chemist’s toolbox.
- Hernandez, Anolan Garcia,Grooms, Gregory M.,El-Alfy, Abir T.,Stec, Jozef
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p. 2163 - 2176
(2017/05/05)
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- Carbamoyloxy derivatives of mutiline and their use as antibacterials
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PCT No. PCT/EP96/05874 Sec. 371 Date Dec. 4, 1998 Sec. 102(e) Date Dec. 4, 1998 PCT Filed Dec. 19, 1996 PCT Pub. No. WO97/25309 PCT Pub. Date Jul. 17, 1997Derivatives of mutiline of formula (1A) and pharmaceutically acceptable salts and derivatives thereof, in which R1 is ethyl or vinyl, Y is a carbamoyloxy group, in which the N-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.
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