Abstract
3,5-Di[(E)-arylidene]-1-[3-(4-methylpiperazin-1-yl)alkyl]piperidin-4-ones 7 a−k were synthesized through dehydrohalogenation of 1-(2-chloroacyl)piperidin-4-ones 5 a−k with N-methylpiperazine (6). High antiproliferation potencies were observed by most of the synthesized agents against both HCT116 (colon) and MCF7 (breast) cancer cell lines relative to the standard references (sunitinib and 5-fluorouracil). The synthesized agents are of dual activity against topoisomerases I and IIα however, with higher efficacy against topoisomerase IIα rather than topoisomerase I. Flow-cytometry cell cycle studies support the observed antiproliferation properties and exhibit the capability of 1-(2-chloroacetyl)-3,5-bis[(E)-4-chlorobenzylidene]piperidin-4-one (5 e) and 3,5-bis[(E)-4-bromobenzylidene]-1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-one (7 g) to arrest the HCT116 cell cycle progression at G1/S and G1 phases, respectively. Noticeable anti-SARS-CoV-2 properties were observed by many synthesized agents. 3,5-Bis[(E)-4-chlorobenzylidene]-1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-one (7 f) is the most effective anti-SARS-CoV-2 synthesized with high SI. Applicability of the highly effective candidates synthesized as antitumor and anti-SARS-CoV-2 is due to the safety observations against normal (RPE1 and VERO-E6) cells. QSAR models validated internally and externally, support their possibility for optimizing more hits/leads.
Original language | English (US) |
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Article number | e202201406 |
Journal | ChemistrySelect |
Volume | 7 |
Issue number | 31 |
DOIs | |
State | Published - Aug 19 2022 |
Keywords
- Antitumor
- Molecular modeling
- Piperazine
- Piperidone
- SARS-CoV-2
- Topoisomerase
ASJC Scopus subject areas
- General Chemistry