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 II alpha however, with higher efficacy against topoisomerase II alpha 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.
ABSTRACT
This report announces the complete genome sequences of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates detected in Egypt. The isolates were obtained from oropharyngeal swab specimens from two Egyptians in Upper and Lower Egypt. Sequence analysis showed mutations that differentiate Egyptian strains from the reference strain 2019-nCoV WHU01.