PMID- 37969920
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240212
IS  - 2251-6581 (Print)
IS  - 2251-6581 (Electronic)
IS  - 2251-6581 (Linking)
VI  - 22
IP  - 2
DP  - 2023 Dec
TI  - Cheminformatics identification of modulators of key carbohydrate-metabolizing 
      enzymes from C. cujete for type-2 diabetes mellitus intervention.
PG  - 1299-1317
LID - 10.1007/s40200-023-01249-7 [doi]
AB  - PURPOSE: The therapeutic use of oral hypoglycaemic agents in the management of 
      type-2 diabetes mellitus (T2DM) is without adverse effects; thus, calls for 
      alternative and novel candidates from natural products in medicinal plants. 
      METHOD: The study explored molecular docking and molecular dynamics (MD) 
      simulation approaches to identify key antidiabetic metabolites from Crescentia 
      cujete. RESULTS: Molecular docking results identified four and/or five best 
      compounds against each target enzyme (alpha-glucosidase, dipeptidyl peptidase-IV, 
      aldose reductase, and protein tyrosine phosphatase-1B (PTP-1B)) implicated in 
      diabetes. The resulting complexes (except against PTP-1B) had higher docking 
      scores above respective standards (acarbose, Diprotin A, ranirestat). The MD 
      simulation results revealed compounds such as benzoic acid (-48.414 kcal/mol) and 
      phytol (-45.112 kcal/mol) as well as chlorogenic acid (-42.978 kcal/mol) and 
      naringenin (-31.292 kcal/mol) had higher binding affinities than the standards 
      [acarbose (-28.248 kcal/mol), ranirestat (-21.042 kcal/mol)] against 
      alpha-glucosidase and aldose reductase, respectively while Diprotin A 
      (-45.112 kcal/mol) and ursolic acid (-18.740 kcal/mol) presented superior binding 
      affinities than the compounds [luteolin (-41.957 kcal/mol and naringenin 
      (-16.518 kcal/mol)] against DPP-IV and PTP-1B respectively. CONCLUSION: While 
      isoflavone (alpha-glucosidase), xylocaine (DPP-IV), luteolin (aldose reductase,) 
      and chlorogenic acid (PTP-1B) were affirmed as the best inhibitors of respective 
      enzyme targets, luteolin, and chlorogenic acid may be suggested and proposed as 
      probable candidates against T2DM and related retinopathy complication based on 
      their structural stability, compactness and affinity for three (DPP-IV, aldose 
      reductase, and PTP-1B) of the four targets investigated. Further studies are 
      warranted in vitro and in vivo on the antihyperglycaemic effects of these drug 
      candidates. SUPPLEMENTARY INFORMATION: The online version contains supplementary 
      material available at 10.1007/s40200-023-01249-7.
CI  - (c) The Author(s) 2023. Springer Nature or its licensor (e.g. a society or other 
      partner) holds exclusive rights to this article under a publishing agreement with 
      the author(s) or other rightsholder(s); author self-archiving of the accepted 
      manuscript version of this article is solely governed by the terms of such 
      publishing agreement and applicable law.
FAU - Balogun, Fatai Oladunni
AU  - Balogun FO
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
FAU - Singh, Karishma
AU  - Singh K
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
AD  - Department of Nature Conservation, Mangosuthu University of Technology, 
      Mangosuthu, South Africa. ROR: https://ror.org/054r97095. GRID: grid.429399.c. 
      ISNI: 0000 0004 0630 4697
FAU - Rampadarath, Athika
AU  - Rampadarath A
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
FAU - Akoonjee, Ayesha
AU  - Akoonjee A
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
FAU - Naidoo, Kayleen
AU  - Naidoo K
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
FAU - Sabiu, Saheed
AU  - Sabiu S
AD  - Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban 
      University of Technology, P.O. Box 1334, Durban, 4000 South Africa. ROR: 
      https://ror.org/0303y7a51. GRID: grid.412114.3. ISNI: 0000 0000 9360 9165
LA  - eng
PT  - Journal Article
DEP - 20230701
PL  - Switzerland
TA  - J Diabetes Metab Disord
JT  - Journal of diabetes and metabolic disorders
JID - 101590741
PMC - PMC10638353
OTO - NOTNLM
OT  - Chlorogenic acid
OT  - Crescentia cujete
OT  - Isoflavone
OT  - Luteolin
OT  - Molecular dynamics simulation
OT  - Type-2 diabetes mellitus
OT  - Xylocaine
COIS- Competing interestsNo conflicting interest among the authors.
EDAT- 2023/11/16 06:45
MHDA- 2023/11/16 06:46
PMCR- 2023/07/01
CRDT- 2023/11/16 04:26
PHST- 2022/08/16 00:00 [received]
PHST- 2023/06/07 00:00 [accepted]
PHST- 2023/11/16 06:46 [medline]
PHST- 2023/11/16 06:45 [pubmed]
PHST- 2023/11/16 04:26 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - 1249 [pii]
AID - 10.1007/s40200-023-01249-7 [doi]
PST - epublish
SO  - J Diabetes Metab Disord. 2023 Jul 1;22(2):1299-1317. doi: 
      10.1007/s40200-023-01249-7. eCollection 2023 Dec.