PMID- 33769204
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20221013
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 40
IP  - 16
DP  - 2022 Oct
TI  - Anti-glycemic potential of benzophenone thio/semicarbazone derivatives: 
      synthesis, enzyme inhibition and ligand docking studies.
PG  - 7339-7350
LID - 10.1080/07391102.2021.1897045 [doi]
AB  - Inhibition of dipeptidyl peptidase-IV (DPP-IV) has been identified as a promising 
      approach for the treatment of type 2 diabetes mellitus (T2DM). Therefore, 
      development of DPP-IV inhibitors with new chemical scaffold is of utmost 
      importance to medicinal chemistry. In the present study, we identified 
      benzophenone thio- and semicarbazone scaffolds as novel DPP-IV inhibitors. For 
      that purpose, benzophenone thio- and semicarbazone were synthesized through a 
      2-step reaction. These newly synthetic derivatives were characterized by 
      different spectroscopic techniques, including HREI-MS and NMR. whereas 
      stereochemistry of the iminic bond was predicted by NOESY experiments. Thio- and 
      semicarbazones derivatives were evaluated for their DPP-IV inhibitory potential 
      and found to exhibit a good to moderate enzyme inhibitory activity. Most active 
      and non-cytotoxic derivatives were further evaluated for their DPP-IV inhibitory 
      potential in in cellulo model. The binding sites as well as affinity of active 
      compounds for DPP- IV enzyme were predicted by in silico studies, and compared to 
      a standard drug, sitagliptin. Pharmacophore studies of thio- and semicarbazones 
      derivatives 1-29 suggest that substitution of aryl group, particularly a 
      lipophilic substituents at C-4'' of benzene ring, and a hydroxyl at C-4' strongly 
      influenced the DPP-IV inhibitory activity. Compound 9 showed the highest 
      inhibitory activity (IC(50) = 15.0 +/- 0.6 microM), whereas compounds 10, 17, 12, 14 
      and 23 showed a moderate activity with IC(50) values in the range of 
      28.9-39.2 microM. This study identifies thio- and semicarbazones as new classes of 
      DPP-IV inhibitors which may translate into safe and effective therapeutics for a 
      better management of type 2 diabetes.Communicated by Ramaswamy H. Sarma.
FAU - Arshia
AU  - Arshia
AD  - H. E. J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi, Pakistan.
FAU - Fayyaz, Sharmeen
AU  - Fayyaz S
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      Pakistan.
FAU - Shaikh, Muniza
AU  - Shaikh M
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      Pakistan.
FAU - Khan, Khalid Mohammed
AU  - Khan KM
AD  - H. E. J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi, Pakistan.
AD  - Department of Clinical Pharmacy, Institute for Research and Medical Consultations 
      (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
FAU - Choudhary, M Iqbal
AU  - Choudhary MI
AD  - H. E. J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi, Pakistan.
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      Pakistan.
AD  - Department of Chemistry, Faculty of Science and Technology, Universitas 
      Airlangga, Surabaya, Indonesia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210326
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Benzophenones)
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Semicarbazones)
SB  - IM
MH  - Benzophenones/pharmacology/therapeutic use
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - *Dipeptidyl-Peptidase IV Inhibitors/chemistry
MH  - Humans
MH  - Ligands
MH  - Molecular Docking Simulation
MH  - *Semicarbazones
OTO - NOTNLM
OT  - Caco-2 cell line
OT  - Type 2 diabetes mellitus
OT  - benzophenone
OT  - dipeptidyl peptidase-IV (DPP-IV)
OT  - thiosemicarbazone
EDAT- 2021/03/27 06:00
MHDA- 2022/09/14 06:00
CRDT- 2021/03/26 12:27
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2021/03/26 12:27 [entrez]
AID - 10.1080/07391102.2021.1897045 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2022 Oct;40(16):7339-7350. doi: 
      10.1080/07391102.2021.1897045. Epub 2021 Mar 26.