Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Substituted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells

Abstract

Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

“…Our study disclosed the selective growth inhibition of breast cancer cells, MDA-MB-468 corresponded to the 3f compound is associated with apoptosis pathway through ROS generation. Our results are in agreement with the literature (Xiong et al, 2019) that reported a novel thiazolyl substituted bis-pyrazole oxime compound selectively inhibited proliferation of colorectal cancer HCT116 cells by inducing apoptosis pathway through the promotion of intracellular ROS level. The therapeutic impact of a Pyrazole compound on angiogenesis in human umbilical vein endothelial cells (HUVECs) was studied by Zhang et al, (2011).…”

Convenient Synthesis of N-Heterocycle-Fused Tetrahydro-1,4-diazepinones

“…In this work, the formation of the desired 1-(oxiran-2-ylmethyl)-3-aryl-1H-pyrazole-5-carboxylates by alkylation of easily accessible NH-pyrazoles [48] with 2-(chloromethyl)oxirane was optimized using 1a as a model compound. As shown in Table 1, reaction outcome is highly dependent on the choice of the base and the solvent.…”

“…Synthetic Procedures 3.2.1. General Procedure for Synthesis of Starting 3(5)-Aryl-1H-pyrazole-5(3)-carboxylates (1a-h) [48,65] To a 0.5 M solution of sodium ethoxide (1.1 eq) in ethanol, appropriate acetophenone (1 eq) and diethyl oxalate (1 eq) were added, and the resulting mixture was stirred at room temperature for 16 h in an inert atmosphere. Upon completion, the reaction mixture was quenched with 1 M HCl solution until neutral pH and extracted with ethyl acetate.…”

Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure–activity relationships

“…Synthesis of ethyl 3(5)-aryl-4-bromo-1H-pyrazole-5(3)carboxylates 3a-c (ref. 43). An appropriate pyrazole 2a-c (1 eq.)…”