title: Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors.
abstract: In the current work, new benzodioxole-based dithiocarbamate derivatives were synthesized via the reaction of N-(1,3-benzodioxol-5-ylmethyl)-2-chloroacetamide with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. These derivatives were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. N-(1,3-Benzodioxol-5-ylmethyl)-2-[4-(4-nitrophenyl)-1-piperazinylthiocarbamoylthio]acetamide (10) can be identified as the most promising anticancer agent against C6 cell line due to its notable inhibitory effect on C6 cells with an IC50value of 23.33 ± 7.63 μg/mL when compared with cisplatin (IC50= 19.00 ± 5.29 μg/mL). On the other hand, compound 10 did not show any significant cytotoxic activity against A549 cell line. The compounds were also tested for their in vitro inhibitory effects on hCA-I and hCA-II. Generally, the tested compounds were more effective on CAs than acetazolamide, the reference agent. Among these compounds, N-(1,3-benzodioxol-5-ylmethyl)-2-[(morpholinyl)thiocarbamoylthio]acetamide (3) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(thiomorpholinyl)thiocarbamoylthio]acetamide (4) were found to be the most effective compounds on hCA-I with IC50values of 0.346 nM and 0.288 nM, and hCA-II with IC50values of 0.287 nM and 0.338 nM, respectively.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: mdaltintop@anadolu.edu.tr.
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altıntop
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors.forename: Belgin
authors.initials: B
authors.lastname: Sever
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors.forename: Gülşen
authors.initials: G
authors.lastname: Akalın Çiftçi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey.
authors.forename: Kaan
authors.initials: K
authors.lastname: Kucukoglu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Özdemir
authors.affiliation: Department of Nano-Science and Nano-Engineering, Faculty of Engineering, Ataturk University, 25240, Erzurum, Turkey.
authors.forename: Seyedeh Sara
authors.initials: SS
authors.lastname: Soleimani
authors.affiliation: Department of Food Technology, Erzurum Vocational Training School, Ataturk University, 25240, Erzurum, Turkey.
authors.forename: Hayrunnisa
authors.initials: H
authors.lastname: Nadaroglu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors.forename: Zafer Asım
authors.initials: ZA
authors.lastname: Kaplancıklı
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D052117:Benzodioxoles / Q000737:chemistry; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D002257:Carbonic Anhydrase Inhibitors; D013859:Thiocarbamates; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Benzodioxole; Cancer; Dithiocarbamate; Human carbonic anhydrase