Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.
Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 μM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.
a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
Cem
C
Yamali
a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
Halise Inci
HI
Gul
b Division of Pharmacology , Meikai University School of Dentistry , Sakado , Japan , and.
Hiroshi
H
Sakagami
c Neurofarba Department and Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Florence , Italy.
Claudiu T
CT
Supuran
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006219:Halogens / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D047188:Chalcones; D006219:Halogens; D007527:Isoenzymes; D008352:Mannich Bases; D010636:Phenols; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
Carbonic anhydrase; Mannich bases; chalcone; cytotoxicity; phenol