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Abstract

EVALUATION OF ANTIPROLIFERATIVE POTENCY AND INDUCED BIOCHEMICAL PARAMETERS OF NOVEL PYRIDINE DERIVATIVES AGAINST LEUKEMIA, LUNG, BREAST AND COLON CANCER CELL LINES

Abdel Mohsen Soliman*, Hala F. Abdelhamid, Joanna Wietrzyk, Agata Pawlik

ABSTRACT

On the basis of monitoring the inhibition of the growth of human cancer cells, a series of novel Pyridine derivatives reacted with different phosphorus nucleophiles to afford novel phosphanylidene compounds that thought to possess a broader spectrum of antitumor activity and fewer toxic side effects than traditional anticancer drugs were synthesized. Nine of the newly synthesized compounds (5a, 5b, 6, 12a, 12b, 12d, 15b, 16, 21) were subjected to a screening system for investigation of their antiproliferative potency against human promyelocytic leukemia (HL-60) in comparison to the traditional anticancer drugs: cisplatin (CIS) and doxorubicin (DOX). Results showed that the highest in vitro cytotoxic activity against HL-60 cell line (IC50 lower than 12 μg/ml) revealed compounds: 5a, 6, 5b. Those compounds were chosen for testing their activity towards lung (A549), breast (T-47D) and colon (LoVo) cancer cell lines. Compound 6 showed the highest potency against all tested cancer cells. Moreover, the biochemical effects of the selected Pyridine derivatives on some enzymes such as aspartate and alanine aminotransferases (AST and ALT) and alkaline phosphatase (ALP), in addition to albumin, globulins, creatinine, total lipids, cholesterol, triglycerides and bilirubin in serum of mice were studied in comparison to Cisplatin and Doxorubicin. On the other hand, results of the biochemical investigations indicated that Cisplatin and Doxorubicin caused significant changes in the level of all parameters tested while treatment with the selected compounds showed slight, moderate or no significant changes. In this study, we have identified phosphanylidene derivatives as a novel class of compounds possessing anti-proliferative activity. The lead compounds 5a and 6 were the most potent in the biological assay employed (e.g.: similar or improved growth inhibition potential as compared to the reference anticancer drugs cisplatin and doxorubicin).These experimental findings may provide support for the use of these novel compounds as anticancer agents.

Keywords: Phosphanylidene derivatives, Cytotoxic activity, leukemia (HL-60), lung cancer (A549), breast adenocarcinoma (T-47D), human colon cancer cells (LoVo).


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