Antitumor Activity of Some Pyridinecarboxy Acid Compounds in Tumor Cell Cultures

Abstract

We studied the antitumor activity of two compounds - derivatives of pyridinecarboxylic acids with laboratory codes LHT-13-19 and LHT-17-19 in two cancer cell cultures: colon HT29 and estrogen-sensitive breast cancer MCF-7. Сompounds were synthesized in the department of chemistry, technology of synthetic drugs and analytical control of VNС BAV (Russia). A possible mechanism for the development of secondary chemoresistance was determined on the organoid model of triple-negative breast cancer, provided to us by scientists from the FGBI “N.N. Dmitry Rogachev" of the Ministry of Health of Russia. Both compounds were shown to be cytotoxic against two human neoplasias with an inhibitory concentration of 1.3 × 10-7 for substance LHT-17-19 and LHT-13-19 – 7.6 × 10-3 M for colon cancer HT29 and 1.6×10-5 (LHT-17-19) and 3.8×1 (LHT-13-19) for MCF-7 breast cancer. During the formation of secondary resistance of triple-negative breast cancer cells to LHT-13-19, the reverse transport of compound molecules is activated, as evidenced by the increase in the concentration of the substance in the cultivation medium after washing the three-dimensional culture. Under the same experimental conditions, although secondary resistance to LHT-17-19 is formed, no efflux of molecules into the medium is observed, which indicates that in this case other mechanisms not related to reverse transport may be involved.