title: Carbonic anhydrase inhibition and cytotoxicity studies of Mannich base derivatives of thymol.
abstract: Mannich bases of thymol were synthesized. The aminomethylation reaction was realised in the ortho position of the phenol for compounds 2 (dipropylamine), 3 (benzylamine), and 4 (dibenzylamine) while it was from para position for 1 (dimethylamine), 5 (piperidine), 6 (morpholine) and 7 (N-methylpiperazine). The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were asssessed against hCA I and hCA II. All compounds moderately inhibited hCA I and hCA II. The cytotoxicity of the compounds against four human oral squamous cell carcinoma cell lines were compared those against three normal oral cells. Tumor specificity values were about 2 or slightly more for the compounds 2, 3, 4, 5 and 6. Compound 2 showed cytostatic activity against OSCC cell lines at 16 to 32-fold lower concentrations as compared with normal cells. This suggests that compound 2 can be considered as cytotoxicity enhancing drug candidate for further investigations.
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .
authors: Halise
authors: H
authors: Inci Gul
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .|b Polo Scientifico, Laboratorio di Chimica Bioinorganica, Universita degli Studi di Firenze , Sesto Fiorentino , Italy , and.
authors: Cem
authors: C
authors: Yamali
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .
authors: Asiye
authors: A
authors: Tugce Yasa
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .
authors: Elif
authors: E
authors: Unluer
authors: c Division of Pharmacology , Meikai University School of Dentistry , Sakado , Saitama , Japan.
authors: Hiroshi
authors: H
authors: Sakagami
authors: b Polo Scientifico, Laboratorio di Chimica Bioinorganica, Universita degli Studi di Firenze , Sesto Fiorentino , Italy , and.
authors: Muhammet
authors: M
authors: Tanc
authors: b Polo Scientifico, Laboratorio di Chimica Bioinorganica, Universita degli Studi di Firenze , Sesto Fiorentino , Italy , and.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008352:Mannich Bases / Q000737:chemistry*; D009062:Mouth Neoplasms / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013943:Thymol / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D008352:Mannich Bases; D013943:Thymol
keywords: Carbonic anhydrase; Mannich bases; cytotoxicity; phenol; thymol