Протипухлинна активність похідного дигідропіролу на моделі раку товстої кишки щурів, індукованого диметилгідразином

Abstract

In vivo studies of antitumor activity of dihydropyrrol derivative 5-amino-4-(1,3-benzothiazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D1) on model of 1,2-dimethylhydrazine-induced colon cancer in rats were performed. D1 causes a decrease in tumor number and tumor lesions total area by 41%, which is comparable with the effect of typical antineoplastic drug 5-fluorouracil (tumor number and tumor total area decrease by 50% and 43%, respectively). D1 possesses more gentle effect on the relatively healthy (with no tumors) rat intestinal mucosa compared with 5-fluorouracil. Also, this compound reduces carcinogen-induced microvascular disorders and inflammation. It does not suppress the proliferation of crypt cells, contributes to partial normalization of colon and rectum mucosa morpho-functional state. In contrast, 5-fluorouracil causes microvascular changes and inflammation aggravation, inhibits normal crypt cells proliferation by 31–45%. D1 under concomitant action with 5-fluorouracil reduces the toxic effect of 5-FU on the intestinal mucosa, resulting in less expressed inflammation and partial recovery of morpho-functional state of colon mucosa. Antitumor effects of these compounds are not cumulative, and decrease of tumor number is by 46% and tumor total area – by 54%. Keywords: dihydropyrrol derivate, 5-fluorouracil, jejunum, colon, rectum, colon carcinogenesis.