Çağla Begüm APAYDIN, Gozde HASBAL ÇELİKOK, Tuğba YILMAZ ÖZDEN, Gökçe CİHAN-ÜSTÜNDAĞ

Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors

Background and Aims: Diabetes mellitus is among the major hazards to global public health due to increasing incidence worldwide, and new therapeutic agents are urgently needed for the control of the disease. In this study, a novel series of sulfonamide hydrazones (3a-i) were synthesized and evaluated, in vitro, for α-amylase and α-glucosidase inhibitor activities. Methods: Target compounds were prepared according to a high-yielded synthetic route. The in vitro antidiabetic activity of the compounds was analyzed by evaluating the inhibitory abilities on α-glucosidase and α-amylase enzymes. Acarbose was chosen as a reference in this study.Results: Compounds 3d, 3e, 3g and 3h exhibited better α-glucosidase inhibitory activity compared to reference antidiabetic drug acarbose. Compound 3g was the most active analogue, possessing an IC50 value of 65.27 µg/mL. 3d, 3e, 3g and 3h showed similar α-amylase inhibitory activity compared to acarbose when tested at high concentrations. However, their IC50 values were much higher compared to that of reference acarbose.Conclusion: The most active analogue 3g was found to be two times more active than acarbose. The addition of a bulky group to the 4-position of the cyclohexane ring seemed to have a positive effect on antidiabetic activity. The new hydrazone deriva- tives reported in this study are potentially promising candidates for developing new antidiabetic agents.

Keywords:

Antidiabetic activity Sulfonamide, Hydrazone, α-amylase, α-glucosidase,

PDF

___

Akkurt, M., Türktekin-Çelikesir, S., Cihan-Üstündağ, G., Çapan, G., & Büyükgüngör, O. (2013). N-(4-Ethylcyclohexylidene)-5-fluoro- 3-phenyl-1H-indole-2-carbohydrazide. Acta Crystallographica Section E, E69, 1331. https://doi.org/10.1107/S1600536813020394
Ali, H., Houghton, P. J., & Soumyanath, A. (2006). α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with partic- ular reference to Phyllanthus amarus. Journal of Ethnopharmacology, 107(3), 449–455. https://doi.org/10.1016/j.jep.2006.04.004
Apaydın, Ç.B. (2018). FenoksiasetamidYapısıTaşıyanTiyazolidinonlar Üzer- inde Çalışmalar. (Doctoral dissertation). Retrieved from https://tez.yok. gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=MsUfCzS3veHBGNDkm8m_ BA&no=91GPEzP_U0xS5UJCmhRx8A
Bothon, F. T. D., Debiton, E., Avlessi, F., Forestier, C., Teulade, J. C., & Sohounhloue, D. K. C. (2013). In vitro biological effects of two anti-diabetic medicinal plants used in benin as folk medicine. BMC Complementary and Alternative Medicine, 13(51), 1-8. https:// doi.org/10.1186/1472-6882-13-51
Cihan-Üstündağ, G. & Çapan, G. (2012). Synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents. Molecular Diversity,16, 525-539. https://doi.org/10.1007/ s11030-012-9385-y
Cihan-Üstündağ, Mataracı-Kara, E., & Çapan, G. (2019). Synthe- sis, characterization, antibacterial and antifungal evaluation of novel cyclohexanone benzoylhydrazones. Istanbul Journal of Pharmacy, 49(3), 142-147. https://doi.org/10.26650/Istan- bulJPharm.2019.19022
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J. …Weiss, R. (2015). Type 2 diabetes mellitus. Na- ture Reviews Disease Primers, 1, 1–23. https://doi.org/10.1038/ nrdp.2015.19
Hossain, U., Das, A. K., Ghosh, S., & Sil, P. C. (2020). An overview on the role of bioactive α-glucosidase inhibitors in ameliorating dia- betic complications. Food and Chemical Toxicology, 145, 111738. https://doi.org/10.1016/j.fct.2020.111738
Kocabalkanlı, A.,Cihan-Üstündağ, G., Naesens, L., Mataracı-Kara, E., Nassozi, M., & Çapan, G. (2017). Diclofenac-Based hydrazones and spirothiazolidinones: Synthesis, Characterization, and antimicro- bial properties. Archieve der Pharmazie, 350, e1700010. https://doi. org/10.1002/ardp.201700010
Koçyiğit-Kaymakçıoğlu, B., Elçin, O., Seda, U., Fatma, K., Nathaly, S., Sevim, R., & Dimoglo, A. (2006). Synthesis and characterization of novel hydrazide-hydrazones and the study of their structure-an- tituberculosis activity. European Journal of Medicinal Chemistry, 41(11), 1253–1261. https://doi.org/10.1016/j.ejmech.2006.06.009
Liu, Z., & Ma, S. (2017). Recent Advances in Synthetic α-Glucosidase Inhibitors. ChemMedChem, 12(11), 819–829. https://doi. org/10.1002/cmdc.201700216
Metwally, K. A., Abdel-Aziz, L. M., Lashine, E. S. M., Husseiny, M. I., & Badawy, R. H. (2006). Hydrazones of 2-aryl-quinoline-4-car- boxylic acid hydrazides: Synthesis and preliminary evaluation as antimicrobial agents. Bioorganic and Medicinal Chemistry, 14(24), 8675–8682. https://doi.org/10.1016/j.bmc.2006.08.022
Moldovan, C. M., Oniga, O., Pârvu, A., Tiperciuc, B., Verite, P., Pîrnǎu,
… Pop, R. (2011). Synthesis and anti-inflammatory evalua- tion of some new acyl-hydrazones bearing 2-aryl-thiazole. Euro- pean Journal of Medicinal Chemistry, 46(2), 526–534. https://doi. org/10.1016/j.ejmech.2010.11.032
Montalvo-Gonzalez, R., Montalvo-Gonzalez, J.A., & Ariza-Castolo, A. (2008). Conformational and structural analysis of exocyclic olefins and ketimines by multinuclear magnetic resonance. Magnetic Res- onance in Chemistry, 46, 907-917. https://doi.org/10.1002/mrc.2259
Nasr, T., Bondock, S., & Youns, M. (2014). Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives. Eu- ropean Journal of Medicinal Chemistry, 76, 539–548. https://doi. org/10.1016/j.ejmech.2014.02.026
Padhi, S., Nayak, A.K., & Behera, A. (2020). Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed Pharmaco- ther, 131, 110708. doi:10.1016/j.biopha.2020.110708
Proença, C., Ribeiro, D., Freitas, M., & Fernandes, E. (2021). Flavo- noids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review. Critical Reviews in Food Science and Nutrition, https://doi. org/10.1080/10408398.2020.1862755
Taha, M., Ismail, N. H., Javaid, K., Imran, S., Anouar, E. H., Wadood,
… Choudhary, M. I. (2015). Evaluation of 2-indolcarbohydra- zones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions. Bioorganic Chemistry, 63, 24–35. https://doi.org/10.1016/j.bioorg.2015.09.001
Toniolo, A., Cassani, G., Puggioni, A., Rossi, A., Colombo, A., On- odera, T., & Ferrannini, E. (2019). The diabetes pandemic and as- sociated infections: Suggestions for clinical microbiology. Reviews in Medical Microbiology, 30(1), 1–17. https://doi.org/10.1097/ MRM.0000000000000155
Türktekin-Çelikesir, S., Akkurt, M., Cihan-Üstündağ, G., Çapan, G., & Büyükgüngör, O. (2013). 5-Fluoro-N0-(4-methylcyclohexylidene)- 3-phenyl-1H-indole-2-carbohydrazide. Acta Crystallographica Sec- tion E, E69, 1211–1212. https://doi//10.1107/S1600536813018436
Ulusoy Güzeldemirci, N., Şatana, D., & Küçükbasmacı, Ö. (2015). Synthesis and antimicrobial evaluation of some new hydrazone derivatives of 6-(4-nitrophenyl)imidazo[2,1-b]thiazole-3-aceticac- id hydrazide. Istanbul Journal of Pharmacy, 45(2), 127-138.
Ulusoy Güzeldemirci, N., Pehlivan, E., Halamoğlu, Z., & Koca- balkanli, A. (2016). Synthesis and antiviral activity evaluation of some new cyclohexylidenehydrazide derivatives of 1,3-thiazole core. Marmara Pharmaceutical Journal, 20, 207-215. https://doi. org/10.12991/mpj.20162019913
Wang, G., Chen, M., Wang, J., Peng, Y., Li, L., Xie, Z. Z. … Li, W. (2017). Synthesis, biological evaluation and molecular docking studies of chromone hydrazone derivatives as α-glucosidase inhibitors. Bioorganic and Medicinal Chemistry Letters, 27(13), 2957–2961. https://doi.org/10.1016/j.bmcl.2017.05.007
World Health Organization (2021). WHO Health topics:Diabetes. Re- trieved from https://www.who.int/health-topics/diabetes#tab=tab_1
Zawawi, N. K. N. A., Taha, M., Ahmat, N., Wadood, A., Ismail, N. H., Rahim, F. … Abdullah, N. (2016). Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies. Bioorganic Chemis- try, 64, 29–36. https://doi.org/10.1016/j.bioorg.2015.11.006

ISSN: 2548-0731
Yayın Aralığı: Yılda 3 Sayı
Başlangıç: 1965
Yayıncı: İstanbul Üniversitesi

Arşiv