Synthesis of Some Pyrazolines and Pyrimidines Derived from Polymethoxy Chalcones as Anticancer and Antimicrobial Agents

Abstract

The synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14-17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI(50) MG-MID values of 2.10 and 1.38 µM, respectively), together with moderate cytostatic effects (TGI MG-MID values of 47.9 and 42.7 µM, respectively). Meanwhile, the pyrimidin-2-one 11 showed a noticeable overall tumor growth inhibitory activity, together with high cytostatic and cytotoxic efficacies (GI(50) , TGI and LC(50) MG-MID values of 3.39, 17.4, and 61.7 µM, respectively). On the other hand, compounds 3, 4, 13, 15, 19, 20, and 23 were found to be the most active antimicrobial members in this investigation with a broad spectrum of activity. Compound 23 was four times superior to ampicillin against Pseudomonas aeruginosa. The best antifungal activity was demonstrated by compounds 4, 5, and 11 which possessed almost half the activity of clotrimazole against Candida albicans. Collectively, the obtained biological results suggest that compound 4 could be considered as a possible dual antimicrobial-anticancer agent.

Synthesis of Oxadiazolyl, Pyrazolyl and Thiazolyl Derivatives of Thiophene-2-Carboxamide as Antimicrobial and Anti-HCV Agents

“…The minimal inhibitory concentrations (MIC) of the most active compounds were measured using the twofold serial broth dilution method [39, 40]. The test organisms were grown in their suitable broth: 24 h for bacteria and 48 h for fungi at 37 o C. Twofold serial dilutions of solutions of the test compounds were prepared using 200, 100, 50, 25, and 12.5 µg/mL.…”

“…They were also studied for their in vitro antifungal potential against Candida albicans . The inhibition zones were measured utilizing the cup-diffusion technique [38, 39] and compounds showing reasonable inhibition zones (A ≥13 mm) were further evaluated to determine their minimal inhibitory concentration (MIC) and minimum bacterial concentration (MBC) applying the twofold serial dilution method [39, 40]. Ampicillin was used as antibacterial reference while clotrimazole was used as antifungal standard.…”

Ultrasonics Promoted Synthesis of 5-(Pyrazol-4-yl)-4,5-Dihydropyrazoles Derivatives

“…Cyclization of chalcones, leading to pyridine, pyrimidine and pyrazoline derivatives, has been a developing field within the realm of heterocyclic chemistry for the past several years, because of their ready accessibility and the broad spectrum of biological activity of the products [38][39][40][41][42][43][44]. These observations led us to synthesize chalcones and its corresponding pyrazoline, exploring simple procedures.…”

“…The hydrazines and solvents used, such as, ethanol, dichloromethane, glacial acetic acid and ethyl acetate, were obtained from Merck Chemical Company. The chalcone-like heteroanalogues 1 were obtained according to the methodology described [39,53,54].…”

Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells

“…compounds A-D; Figure 1) 12,21,22 . Encouraged by the above-mentioned findings and in continuation of our efforts linked with discovering and exploring novel lead structures as potent chemotherapeutic agents [23][24][25][26] , it was attempted to synthesize new pyrazolo [3,4-d]pyrimidin-4-ones comprising a variety of substituents at position 6 (E; Figure 1) to be evaluated for their anti-cancer activity. The substituents at position 6 include various pharmacophores and functionalities that are believed to be responsible for the biological significance of some relevant anti-cancer agents such as alkylamino 22,27 together with other pharmacophoric groups that would confer different electronic and lipophilic environment, which would influence the targeted anti-cancer activity.…”