Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study

Muhammad Taha; Maryam Irshad; Syahrul Imran; Sridevi Chigurupati; Manikandan Selvaraj; Fazal Rahim; Nor Hadiani Ismail; Faisal Nawaz; Khalid Mohammed Khan

doi:10.1016/j.ejmech.2017.10.028

Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study

Eur J Med Chem. 2017 Dec 1:141:530-537. doi: 10.1016/j.ejmech.2017.10.028. Epub 2017 Oct 12.

Authors

Muhammad Taha¹, Maryam Irshad², Syahrul Imran³, Sridevi Chigurupati⁴, Manikandan Selvaraj⁵, Fazal Rahim⁶, Nor Hadiani Ismail³, Faisal Nawaz⁷, Khalid Mohammed Khan⁸

Affiliations

¹ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), University of Dammam, Dammam 31441, Saudi Arabia. Electronic address: taha_hej@yahoo.com.
² Department of Chemistry, University of Wah, Quaid Avenue, Wah Cantt 47000, Pakistan; Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
³ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia.
⁵ Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
⁶ Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan.
⁷ Department of Chemistry, University of Wah, Quaid Avenue, Wah Cantt 47000, Pakistan.
⁸ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

PMID: 29102178
DOI: 10.1016/j.ejmech.2017.10.028

Abstract

Piperazine Sulfonamide analogs (1-19) have been synthesized, characterized by different spectroscopic techniques and evaluated for α-amylase Inhibition. Analogs 1-19 exhibited a varying degree of α-amylase inhibitory activity with IC₅₀ values ranging in between 1.571 ± 0.05 to 3.98 ± 0.397 μM when compared with the standard acarbose (IC₅₀ = 1.353 ± 0.232 μM). Compound 1, 2, 3 and 7 showed significant inhibitory effects with IC₅₀ value 2.348 ± 0.444, 2.064 ± 0.04, 1.571 ± 0.05 and 2.118 ± 0.204 μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.

Keywords: Molecular docking; Piperazine; SAR; Sulfonamide; Synthesis; α-Amylase inhibition.

MeSH terms

Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacology*
Molecular Docking Simulation
Molecular Structure
Piperazine
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*
alpha-Amylases / antagonists & inhibitors*
alpha-Amylases / metabolism

Substances

Enzyme Inhibitors
Hypoglycemic Agents
Piperazines
Sulfonamides
Piperazine
alpha-Amylases