PMID- 37570832
OWN - NLM
STAT- MEDLINE
DCOM- 20230814
LR  - 20230814
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 28
IP  - 15
DP  - 2023 Aug 3
TI  - Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development 
      of Antidiabetic Agents.
LID - 10.3390/molecules28155860 [doi]
LID - 5860
AB  - This article sheds light on the various scaffolds that can be used in the 
      designing and development of novel synthetic compounds to create DPP-4 inhibitors 
      for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a 
      variety of scaffolds with high DPP-4 inhibition activity, such as 
      pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and 
      esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, beta-carbonyl 
      1,2,4-triazole, and quinazoline motifs. The article further explains that the 
      potential of the compounds can be increased by substituting atoms such as 
      fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, 
      saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction 
      with specific residues was studied to gain a better understanding of the active 
      sites of DPP-4. The structural activities of the various scaffolds against DPP-4 
      were further illustrated by their inhibitory concentration (IC(50)) values. 
      Additionally, various synthesis schemes were developed to make several 
      commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and 
      omarigliptin. In conclusion, the use of halogenated scaffolds for the development 
      of DPP-4 inhibitors is likely to be an area of increasing interest in the future.
FAU - Mathur, Vishal
AU  - Mathur V
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Alam, Ozair
AU  - Alam O
AUID- ORCID: 0000-0003-0322-2509
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Siddiqui, Nadeem
AU  - Siddiqui N
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Jha, Mukund
AU  - Jha M
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Manaithiya, Ajay
AU  - Manaithiya A
AUID- ORCID: 0000-0001-5220-2606
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Bawa, Sandhya
AU  - Bawa S
AD  - Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical 
      Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New 
      Delhi 110062, India.
FAU - Sharma, Naveen
AU  - Sharma N
AD  - Division of Bioinformatics, Indian Council of Medical Research, New Delhi 110029, 
      India.
FAU - Alshehri, Sultan
AU  - Alshehri S
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, 
      Ad Diriyah 13713, Saudi Arabia.
FAU - Alam, Prawez
AU  - Alam P
AUID- ORCID: 0000-0002-7632-3426
AD  - Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz 
      University, Al-Kharj 11942, Saudi Arabia.
FAU - Shakeel, Faiyaz
AU  - Shakeel F
AUID- ORCID: 0000-0002-6109-0885
AD  - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 
      11451, Saudi Arabia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230803
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - I6B4B2U96P (Vildagliptin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Humans
MH  - *Dipeptidyl-Peptidase IV Inhibitors/chemistry
MH  - Hypoglycemic Agents/chemistry
MH  - Vildagliptin
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Sitagliptin Phosphate
MH  - Structure-Activity Relationship
PMC - PMC10420935
OTO - NOTNLM
OT  - DPP-4 inhibitors
OT  - SAR
OT  - bio-activity
OT  - heterocyclic scaffolds
COIS- The authors declare no conflict of interest.
EDAT- 2023/08/12 10:46
MHDA- 2023/08/14 06:42
PMCR- 2023/08/03
CRDT- 2023/08/12 01:18
PHST- 2023/05/13 00:00 [received]
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2023/08/14 06:42 [medline]
PHST- 2023/08/12 10:46 [pubmed]
PHST- 2023/08/12 01:18 [entrez]
PHST- 2023/08/03 00:00 [pmc-release]
AID - molecules28155860 [pii]
AID - molecules-28-05860 [pii]
AID - 10.3390/molecules28155860 [doi]
PST - epublish
SO  - Molecules. 2023 Aug 3;28(15):5860. doi: 10.3390/molecules28155860.