Urease inhibition and anticancer activity of novel polyfunctional 5,6-dihydropyridine derivatives and their structure-activity relationship

Abstract

A novel series of tricyano substituted polyfunctional 5,6-dihydropyridine 8a-n bearing functionalized aromatic rings at C-4 and C-6 position have been prepared from (αmethylbenzylidene) malononitriles in good to excellent yields (52-98%) in solvent free conditions. All the synthesized compounds (8a-n) were evaluated for their in vitro urease inhibition and anticancer activity against prostate cancer (PC3) and Hela cell lines. Compound 8k (4,6-bis(4-methoxyphenyl)-5,6-dihydropyridin) showed slightly better urease inhibitory potential (IC50 = 20.47 µM) as compared to standard thiourea (IC50 = 21 µM). Whilst in the case of anticancer studies the compound 8a 2-(4,6-bis(4-bromophenyl)-6-methyl-5,6dihydropyridin found to be most active (IC50 = 4.40 and 8.80 µM) among the series when compared with standard doxorubicin 4 (IC50 = 0.91 and 3.

Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

“…Urease is an enzyme which converts urea to ammonium carbonate and is used as a diagnostic tool to establish the presence of different pathogens in the urinary and gastrointestinal tract [20]. The percentage activity values of urease enzyme of compounds 4a – d were measured at 50 µg/mL and 250 µg/mL (Table 5), whereas, for compounds 4e – g , the percentage activity values of urease enzyme were measured at 15, 40 and 80 µg/mL, respectively (Table 6).…”

“…Thiourea was used as standard inhibitor of urease [20]. The EZ-fit kinetic data base was used to determine IC 50 values [30].…”

Antimicrobial and Antitumor Activity of Enantiopure Pybox–Osmium Complexes

“…Complex 6 is the most‐active osmium complex with an IC 50 value of 2.7 ± 0.3 μ M . This micromolar value is in the order of magnitude of the IC 50 value of doxorubicin (3.1 ± 0.20 μ M ),26 an antitumor drug widely used in clinical practice. The high activity of 6 agrees with the results obtained for the ruthenium complexes trans ‐[RuCl 2 {( R , R )‐Ph‐pybox}(1‐PhCH 2 ‐PTA)] + and trans ‐[RuCl 2 {( S , S )‐ i Pr‐pybox}(1‐PhCH 2 ‐PTA)] + ; these complexes bearing 1‐PhCH 2 ‐PTA show greater apoptotic activity (21 and 12 %, respectively) than trans ‐[RuCl 2 {( R , R )‐Ph‐pybox}(1‐R‐PTA)] + and trans ‐[RuCl 2 {( S , S )‐ i Pr‐pybox}(1‐R‐PTA)] + (R = H, CH 3 , or CH 2 C≡CH), which showed a rather weak ability to promote apoptosis (less than 10 % at 100 μ M ) 4.…”