Synthesis and anticancer activity of mitotic-specific 3,4-dihydropyridine-2(1H)-thiones was written by Nska, Magdalena Peruzy;Borzyszkowska-Ledwig, Aleksandra;Sosnicki, Jacek G.;Struk, Lukasz;Idzik, Tomasz J.;Maciejewska, Gabriela;Skalski, Lukasz;Piotrowska, Katarzyna;Lukasik, Pawel;Drozdzik, Marek;Kurzawski, Mateusz. And the article was included in International Journal of Molecular Sciences in 2021.Formula: C11H9NO This article mentions the following:
Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds For this purpose structural modifications of the previously characterized pyridine analog I were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship anal. of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione II with promising antiproliferative activity (IC50 equal 1.71 ± 0.58μM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely I, III, and II showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analog with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells. In the experiment, the researchers used many compounds, for example, 5-Phenylpyridin-2-ol (cas: 76053-45-7Formula: C11H9NO).
5-Phenylpyridin-2-ol (cas: 76053-45-7) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Formula: C11H9NO