Research Article
BibTex RIS Cite

Design, Synthesis, Biological Evaluation and Docking, ADME Studies of Novel Phenylsulfonyl Piperazine Analogues as α-Amylase Inhibitors

Year 2024, Volume: 45 Issue: 2, 268 - 273, 30.06.2024

Kerem Buran

https://doi.org/10.17776/csj.1401967

Abstract

Diabetes mellitus (DM) stands as one of the most widespread diseases encountered today. It is primarily characterized by diminished insulin levels and heightened blood glucose concentrations. Inhibition of the α-amylase enzyme plays a pivotal role in the management of diabetes mellitus. Piperazine and sulfonamide groups are recognized for their extensive range of biological effects. The current study involved synthesizing five phenylsulfonyl piperazine derivatives. An evaluation of their α-amylase inhibitory capacities was conducted. Phenylsulfonyl piperazine derivatives (compounds 1-5) exhibited notable α-amylase enzymatic inhibition, with compound 4 showing the most substantial potential for inhibition. The inhibitory percentage of compound 4 (80.61±0.62) surpassed that of the standard drug acarbose (78.81±0.02). The molecular docking studies identified compound 4 as possessing the most substantial inhibitory effect on the α-amylase enzyme, with notable binding energy -8.2 kcal/mol. This compound exhibited specific interactions, including π-π stacking and π-anion interactions with key enzyme residues, solidifying its role as a potent inhibitor

Keywords

Diabetes mellitus α-Amylase Piperazine Sulfonamide

Supporting Institution

University of Health Sciences, unit of scientific research project (BAP)

Project Number

2020/040

References

  • [1] Mittal K.R., Mishra R., Sharma V., Mishra I., 1,3,4-Thiadiazole: A Versatile Scaffold for Drug Discovery [Internet]. Vol. 21, Letters in Organic Chemistry, 21 (2024) 400–413.
  • [2] Mishra R., Sharma P.K., Verma P.K., Tomer I., Mathur G., Dhakad P.K., Biological Potential of Thiazole Derivatives of Synthetic Origin, J. Heterocycl Chem., 54(4) (2017) 2103-2116.
  • [3] Mishra I., Chandra P., Sachan N., Thiazole Derivatives as RORγt Inhibitors: Synthesis, Biological Evaluation, and Docking Analysis, Letters in Drug Design & Discovery, 21 (2024) 905–17.
  • [4] Mishra R., Kumar N., Mishra I., Sachan N., A Review on Anticancer Activities of Thiophene and Its Analogs, Mini-Reviews in Medicinal Chemistry. 20 (2020) 1944–1965.
  • [5] Mittal K.R., Purohit P., Quinoline-3-carboxylate Derivatives: A New Hope as an Antiproliferative Agent, Anti-Cancer Agents in Medicinal Chemistry. 20 (2020) 1981–1991.
  • [6] Vitaku E, Smith DT, Njardarson JT. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J Med Chem [Internet]. 2014 Dec 26;57(24):10257–74.
  • [7] Mukherjee D., Mukhopadhyay A., Bhat K.S., Shridhara A.M., Rao K.S., Synthesis, characterization and anticonvulsant activity of substituted 4- chloro-2-(4-piperazin-1-YL) quinazolines, Int. J. Pharm. Sci., 6(5) (2014) 567–571.
  • [8] Kálai T., Khan M., Balog M., Kutala V.K., Kuppusamy P., Hideg K., Structure-activity studies on the protection of Trimetazidine derivatives modified with nitroxides and their precursors from myocardial ischemia-reperfusion injury, Bioorg Med Chem., 14(16) (2006) 5510–5516.
  • [9] Buran K., Reis R., Sipahi H., Önen Bayram F.E., Piperazine and piperidine-substituted 7-hydroxy coumarins for the development of anti-inflammatory agents, Arch. Pharm. (Weinheim) 354(7) (2021) 2000354.
  • [10] Buran K., Bua S., Poli G., Bayram F.E.Ö., Tuccinardi T., Supuran C.T., Novel 8-substituted coumarins that selectively inhibit human carbonic anhydrase IX and XII, Int. J. Mol. Sci., 20(5) (2019).
  • [11] Taha M., Irshad M., Imran S., Chigurupati S., Selvaraj M., Rahim F., Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study, Eur. J. Med. Chem., 141 (2017) 530–537.
  • [12] Finch R.A., Shyam K., Penketh P.G., Sartorelli A.C., 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): A novel sulfonylhydrazine prodrug with bbroad-spectrum antineoplastic activity, Cancer Res., 61(7) (2001) 3033–3038.
  • [13] Ignat A., Zaharia V., Mogoşan C., Palibroda N., Cristea C., Silaghi-Dumitrescu L., Heterocycles 25. Microwave assisted synthesis of some p-toluensulfonyl- hydrazinothiazoles with analgesic and anti-inflammatory activity, Farmacia, 58(3) (2010) 290–302.
  • [14] Goldstein I., Lue T.F., Padma-Nathan H., Rosen R.C., Steers W.D., Wicker P.A., Oral Sildenafil in the Treatment of Erectile Dysfunction, New England Journal of Medicine, 338(20) 1998 1397–404.
  • [15] Fowler M.J., Microvascular and Macrovascular Complications of Diabetes, Clinical Diabetes, 26(2) 2008 77–82.
  • [16] Dehghan M., Ghorbani F., Najafi S., Ravaei N., Karimian M., Kalhor K., Progress toward molecular therapy for diabetes mellitus: A focus on targeting inflammatory factors, Diabetes Res. Clin. Pract., 189 (2022) 109945.
  • [17] Alqahtani A.S., Hidayathulla S., Rehman M.T., Elgamal A.A., Al-Massarani S., Razmovski-Naumovski V., Alpha-amylase and alpha-glucosidase enzyme inhibition and antioxidant potential of 3-oxolupenal and katononic acid isolated from Nuxia oppositifolia, Biomolecules, 10(1) (2020) 61.
  • [18] Gunawan-Puteri M.D.P.T., Kato E., Kawabata J., α-Amylase inhibitors from an Indonesian medicinal herb, Phyllanthus urinaria, J. Sci. Food Agric., 92(3) (2012) 606–609.
  • [19] Williams L.K., Zhang X., Caner S., Tysoe C., Nguyen N.T., Wicki J., The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif., Nat. Chem. Biol., 11(9) (2015) 691–696.
  • [20] Kumar Parai M., Panda G., Srivastava K., Kumar Puri S., Design, synthesis and antimalarial activity of benzene and isoquinoline sulfonamide derivatives, Bioorg Med. Chem. Lett., 18(2) (2008) 776–781.
  • [21] Balan K., Ratha P., Prakash G, Viswanathamurthi P., Adisakwattana S., Palvannan T., Evaluation of invitro α-amylase and α-glucosidase inhibitory potential of N2O2 schiff base Zn complex, Arabian Journal of Chemistry, 10(5) (2017) 732–738.
  • [22] Daina A., Michielin O., Zoete V., SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7 (2017) 1–13.
  • [23] Daina A., Zoete V., A Boiled-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules, Chem. Med. Chem., 11(11) (2016) 1117–1121.

Year 2024, Volume: 45 Issue: 2, 268 - 273, 30.06.2024

Kerem Buran

https://doi.org/10.17776/csj.1401967

Abstract

Project Number

2020/040

References

  • [1] Mittal K.R., Mishra R., Sharma V., Mishra I., 1,3,4-Thiadiazole: A Versatile Scaffold for Drug Discovery [Internet]. Vol. 21, Letters in Organic Chemistry, 21 (2024) 400–413.
  • [2] Mishra R., Sharma P.K., Verma P.K., Tomer I., Mathur G., Dhakad P.K., Biological Potential of Thiazole Derivatives of Synthetic Origin, J. Heterocycl Chem., 54(4) (2017) 2103-2116.
  • [3] Mishra I., Chandra P., Sachan N., Thiazole Derivatives as RORγt Inhibitors: Synthesis, Biological Evaluation, and Docking Analysis, Letters in Drug Design & Discovery, 21 (2024) 905–17.
  • [4] Mishra R., Kumar N., Mishra I., Sachan N., A Review on Anticancer Activities of Thiophene and Its Analogs, Mini-Reviews in Medicinal Chemistry. 20 (2020) 1944–1965.
  • [5] Mittal K.R., Purohit P., Quinoline-3-carboxylate Derivatives: A New Hope as an Antiproliferative Agent, Anti-Cancer Agents in Medicinal Chemistry. 20 (2020) 1981–1991.
  • [6] Vitaku E, Smith DT, Njardarson JT. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J Med Chem [Internet]. 2014 Dec 26;57(24):10257–74.
  • [7] Mukherjee D., Mukhopadhyay A., Bhat K.S., Shridhara A.M., Rao K.S., Synthesis, characterization and anticonvulsant activity of substituted 4- chloro-2-(4-piperazin-1-YL) quinazolines, Int. J. Pharm. Sci., 6(5) (2014) 567–571.
  • [8] Kálai T., Khan M., Balog M., Kutala V.K., Kuppusamy P., Hideg K., Structure-activity studies on the protection of Trimetazidine derivatives modified with nitroxides and their precursors from myocardial ischemia-reperfusion injury, Bioorg Med Chem., 14(16) (2006) 5510–5516.
  • [9] Buran K., Reis R., Sipahi H., Önen Bayram F.E., Piperazine and piperidine-substituted 7-hydroxy coumarins for the development of anti-inflammatory agents, Arch. Pharm. (Weinheim) 354(7) (2021) 2000354.
  • [10] Buran K., Bua S., Poli G., Bayram F.E.Ö., Tuccinardi T., Supuran C.T., Novel 8-substituted coumarins that selectively inhibit human carbonic anhydrase IX and XII, Int. J. Mol. Sci., 20(5) (2019).
  • [11] Taha M., Irshad M., Imran S., Chigurupati S., Selvaraj M., Rahim F., Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study, Eur. J. Med. Chem., 141 (2017) 530–537.
  • [12] Finch R.A., Shyam K., Penketh P.G., Sartorelli A.C., 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): A novel sulfonylhydrazine prodrug with bbroad-spectrum antineoplastic activity, Cancer Res., 61(7) (2001) 3033–3038.
  • [13] Ignat A., Zaharia V., Mogoşan C., Palibroda N., Cristea C., Silaghi-Dumitrescu L., Heterocycles 25. Microwave assisted synthesis of some p-toluensulfonyl- hydrazinothiazoles with analgesic and anti-inflammatory activity, Farmacia, 58(3) (2010) 290–302.
  • [14] Goldstein I., Lue T.F., Padma-Nathan H., Rosen R.C., Steers W.D., Wicker P.A., Oral Sildenafil in the Treatment of Erectile Dysfunction, New England Journal of Medicine, 338(20) 1998 1397–404.
  • [15] Fowler M.J., Microvascular and Macrovascular Complications of Diabetes, Clinical Diabetes, 26(2) 2008 77–82.
  • [16] Dehghan M., Ghorbani F., Najafi S., Ravaei N., Karimian M., Kalhor K., Progress toward molecular therapy for diabetes mellitus: A focus on targeting inflammatory factors, Diabetes Res. Clin. Pract., 189 (2022) 109945.
  • [17] Alqahtani A.S., Hidayathulla S., Rehman M.T., Elgamal A.A., Al-Massarani S., Razmovski-Naumovski V., Alpha-amylase and alpha-glucosidase enzyme inhibition and antioxidant potential of 3-oxolupenal and katononic acid isolated from Nuxia oppositifolia, Biomolecules, 10(1) (2020) 61.
  • [18] Gunawan-Puteri M.D.P.T., Kato E., Kawabata J., α-Amylase inhibitors from an Indonesian medicinal herb, Phyllanthus urinaria, J. Sci. Food Agric., 92(3) (2012) 606–609.
  • [19] Williams L.K., Zhang X., Caner S., Tysoe C., Nguyen N.T., Wicki J., The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif., Nat. Chem. Biol., 11(9) (2015) 691–696.
  • [20] Kumar Parai M., Panda G., Srivastava K., Kumar Puri S., Design, synthesis and antimalarial activity of benzene and isoquinoline sulfonamide derivatives, Bioorg Med. Chem. Lett., 18(2) (2008) 776–781.
  • [21] Balan K., Ratha P., Prakash G, Viswanathamurthi P., Adisakwattana S., Palvannan T., Evaluation of invitro α-amylase and α-glucosidase inhibitory potential of N2O2 schiff base Zn complex, Arabian Journal of Chemistry, 10(5) (2017) 732–738.
  • [22] Daina A., Michielin O., Zoete V., SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7 (2017) 1–13.
  • [23] Daina A., Zoete V., A Boiled-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules, Chem. Med. Chem., 11(11) (2016) 1117–1121.
There are 23 citations in total.

Details

Primary Language English
Subjects Enzymes, Pharmaceutical Chemistry
Journal Section Natural Sciences
Authors

Kerem Buran 0000-0002-7783-7533

Project Number 2020/040
Publication Date June 30, 2024
Submission Date December 8, 2023
Acceptance Date June 13, 2024
Published in Issue Year 2024Volume: 45 Issue: 2

Cite

APA Buran, K. (2024). Design, Synthesis, Biological Evaluation and Docking, ADME Studies of Novel Phenylsulfonyl Piperazine Analogues as α-Amylase Inhibitors. Cumhuriyet Science Journal, 45(2), 268-273. https://doi.org/10.17776/csj.1401967
 Download Cover Image