Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors

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Altıntop M. D., Sever B., Akalın Çiftçi G., Kucukoglu K., Özdemir A., Soleimani S. S., ...Daha Fazla

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.125, ss.190-196, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 125
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.ejmech.2016.09.035
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.190-196
  • Anahtar Kelimeler: Dithiocarbamate, Benzodioxole, Cancer, Human carbonic anhydrase, CARBONIC-ANHYDRASE-IX, ANTIGLAUCOMA ACTION, CANCER-THERAPY, PURIFICATION, DOCKING, SERIES
  • Anadolu Üniversitesi Adresli: Evet

Özet

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 IC50 value of 23.33 +/- 7.63 mu g/mL when compared with cisplatin (IC50 = 19.00 +/- 5.29 mu g/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 IC50 values of 0.346 nM and 0.288 nM, and hCA-II with IC50 values of 0.287 nM and 0338 nM, respectively.