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

Year 2022, , 108 - 113, 30.08.2022

Çağla Begüm Apaydın , Gozde Hasbal Çelikok , Tuğba Yılmaz Özden , Gökçe Cihan-üstündağ

https://doi.org/10.26650/IstanbulJPharm.2022.1018698

Abstract

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

Supporting Institution

Scientific Research Projects Coordination Unit of Istanbul University

Project Number

TSA-2020-34930

References

  • 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

Year 2022, , 108 - 113, 30.08.2022

Çağla Begüm Apaydın , Gozde Hasbal Çelikok , Tuğba Yılmaz Özden , Gökçe Cihan-üstündağ

https://doi.org/10.26650/IstanbulJPharm.2022.1018698

Abstract

Project Number

TSA-2020-34930

References

  • 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
There are 27 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Original Article
Authors

Çağla Begüm Apaydın 0000-0001-6703-9389

Gozde Hasbal Çelikok 0000-0002-0216-7635

Tuğba Yılmaz Özden 0000-0003-4426-4502

Gökçe Cihan-üstündağ 0000-0003-0516-6010

Project Number TSA-2020-34930
Publication Date August 30, 2022
Submission Date November 3, 2021
Published in Issue Year 2022

Cite

APA Apaydın, Ç. B., Hasbal Çelikok, G., Yılmaz Özden, T., Cihan-üstündağ, G. (2022). Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors. İstanbul Journal of Pharmacy, 52(2), 108-113. https://doi.org/10.26650/IstanbulJPharm.2022.1018698
AMA Apaydın ÇB, Hasbal Çelikok G, Yılmaz Özden T, Cihan-üstündağ G. Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors. iujp. August 2022;52(2):108-113. doi:10.26650/IstanbulJPharm.2022.1018698
Chicago Apaydın, Çağla Begüm, Gozde Hasbal Çelikok, Tuğba Yılmaz Özden, and Gökçe Cihan-üstündağ. “Design, Synthesis and Biological Evaluation of Novel Sulfonamide Hydrazones As α-Glucosidase and α-Amylase Inhibitors”. İstanbul Journal of Pharmacy 52, no. 2 (August 2022): 108-13. https://doi.org/10.26650/IstanbulJPharm.2022.1018698.
EndNote Apaydın ÇB, Hasbal Çelikok G, Yılmaz Özden T, Cihan-üstündağ G (August 1, 2022) Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors. İstanbul Journal of Pharmacy 52 2 108–113.
IEEE Ç. B. Apaydın, G. Hasbal Çelikok, T. Yılmaz Özden, and G. Cihan-üstündağ, “Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors”, iujp, vol. 52, no. 2, pp. 108–113, 2022, doi: 10.26650/IstanbulJPharm.2022.1018698.
ISNAD Apaydın, Çağla Begüm et al. “Design, Synthesis and Biological Evaluation of Novel Sulfonamide Hydrazones As α-Glucosidase and α-Amylase Inhibitors”. İstanbul Journal of Pharmacy 52/2 (August 2022), 108-113. https://doi.org/10.26650/IstanbulJPharm.2022.1018698.
JAMA Apaydın ÇB, Hasbal Çelikok G, Yılmaz Özden T, Cihan-üstündağ G. Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors. iujp. 2022;52:108–113.
MLA Apaydın, Çağla Begüm et al. “Design, Synthesis and Biological Evaluation of Novel Sulfonamide Hydrazones As α-Glucosidase and α-Amylase Inhibitors”. İstanbul Journal of Pharmacy, vol. 52, no. 2, 2022, pp. 108-13, doi:10.26650/IstanbulJPharm.2022.1018698.
Vancouver Apaydın ÇB, Hasbal Çelikok G, Yılmaz Özden T, Cihan-üstündağ G. Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors. iujp. 2022;52(2):108-13.