RRC ID 64992
著者 Yamali C, Gul HI, Sakagami H, Supuran CT.
タイトル Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.
ジャーナル J Enzyme Inhib Med Chem
Abstract 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.
巻・号 31(sup4)
ページ 125-131
公開日 2016-1-1
DOI 10.1080/14756366.2016.1221825
PMID 27594305
MeSH Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Carbonic Anhydrase I / antagonists & inhibitors Carbonic Anhydrase I / metabolism Carbonic Anhydrase II / antagonists & inhibitors Carbonic Anhydrase II / metabolism Carbonic Anhydrase Inhibitors / chemical synthesis Carbonic Anhydrase Inhibitors / chemistry Carbonic Anhydrase Inhibitors / pharmacology* Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Line Cell Proliferation / drug effects Chalcones / chemical synthesis* Chalcones / chemistry Chalcones / pharmacology* Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Halogens / chemistry Halogens / pharmacology* Humans Isoenzymes / antagonists & inhibitors Isoenzymes / metabolism Mannich Bases / chemical synthesis Mannich Bases / chemistry Mannich Bases / pharmacology Molecular Structure Mouth Neoplasms / drug therapy* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Phenols / chemistry Phenols / pharmacology* Solubility Structure-Activity Relationship
IF 4.673
リソース情報
ヒト・動物細胞 HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902)