Design, Syntheses, and Bioevaluations of Some Novel N(2)-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents.

A series of novel N(2)-acryloylhydrazides 1a-m and a related series of compounds 6a-c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N(1)-(3,4-dimethoxyphenylcarbonyl)-N(2)-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N(2)-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.