Chemical and anticancer activity studies for some 3-chloro-3-chlorosulfenyl-4′-methylspiro[chroman-2,1′-cyclohexane]-4-ones

Abstract

3-Chloro-3-chlorosulfenyl-4′-methylspiro[chroman-2,1′-cyclohexane]-4-one (4) was prepared from the reaction of spiro 4′-methylcyclohexan-1′,2-chroman-4-one (3) with thionyl chloride according to reported method. Furthermore, treatment of compound 4 with potassium iodide gave 1,2-bis (3-chloro-4′-methylspirochroman-2,1′-cyclohexyl-4-one)disulfane (6) in addition to 4,4‴-dimethyltrispiro[cyclohexane-1,2′-chroman-3′,2″-2H-chromeno[3,4-e][1,3,4]-oxadithiin-5″,1‴-cyclohexan]-4′-one (5). The formation of compound 5 could be presumably explained via the formation of unstable intermediate oxo-thioketone A. The formation of the latter intermediate A was confirmed chemically through the thermal reaction of compound 5, or compound 6 with 1,3-homodiene such as: 1,3-cyclohexadiene, isoprene, and 2,3-dimethyl-1,3-butadiene to afford the products 7–9, respectively. The chemical structures of the newly prepared compounds were confirmed by spectroscopic methods (IR, ¹H & ¹³C NMR, and MS). The synthesized compounds were evaluated against lung (A549), prostate (PC3), pancreatic (PACA2), and breast (MDA) cancer cell lines. Compound 3 exhibited prominent cytotoxicity against A549, PC3, and PACA2 cancer cell lines with IC50 values from 12.4 to 16.1 µM, which was comparable or superior to the reference drug (Doxorubicin). Compounds 7–9 showed better cytotoxicity against breast (MDA) cancer cell line than the reference drug (Doxorubicin).

Graphical Abstract

Keywords:

• Chroman-4-one
• chlorosulfenyl chloride
• [1,3,4] oxadithiin
• disulfide
• thiopyran
• anticancer activity

Additional information

Funding

This project is funded by National Research Centre, Dokki, Giza, Egypt [Project Number: 12010101].