Title:Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR
Volume: 25
Author(s): Saniya Shamim, Ozair Alam*, Mukund Jha, Shagufi Nazar, Vishal Mathur, Shaheen Ali, Anam Iliyas, Kailash Chandra, Shaikh Mohd. Aatif Jamil Ahmed, Mohd. Javed Naim and Bushra Parveen
Affiliation:
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical
Education and Research, Jamia Hamdard, New Delhi-110062, India
Keywords:
Type-II diabetes mellitus, dipeptidyl peptidase-IV inhibitors, triazole, molecular docking, structure-activity relationship.
Abstract: Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome;
is increasing at a very fast pace among every group of the population worldwide. It arises
due to the inability of the body to produce enough insulin (the hormone responsible for controlling
blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if
left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy,
neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several
therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase
(DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or
a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes
the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent
insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of
DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this
breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects
of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant
class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials
have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents.
This review highlights the molecular docking studies and structure-activity relationship of potential
synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules
with enhanced efficacy, potency and reduced toxicity profile.
