PMID- 37485551
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231107
IS  - 1439-7633 (Electronic)
IS  - 1439-4227 (Linking)
VI  - 24
IP  - 20
DP  - 2023 Oct 17
TI  - beta-Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet 
      Amyloid Polypeptide.
PG  - e202300395
LID - 10.1002/cbic.202300395 [doi]
AB  - beta-Carboline alkaloids have a variety of pharmacological activities, such as 
      antitumor, antibiosis and antidiabetes. Harmine and harmol are two structurally 
      similar beta-carbolines that occur in many medicinal plants. In this work, we chose 
      harmine and harmol to impede the amyloid fibril formation of human islet amyloid 
      polypeptide (hIAPP) associated with type 2 diabetes mellitus (T2DM), by a series 
      of physicochemical and biochemical methods. The results indicate that harmine and 
      harmol effectively prevent peptide fibril formation and alleviate toxic oligomer 
      species. In addition, both small molecules exhibit strong binding affinities with 
      hIAPP mainly through hydrophobic and hydrogen bonding interactions, thus reducing 
      the cytotoxicity induced by hIAPP. Their distinct binding pattern with hIAPP is 
      closely linked to the molecular configuration of the two small molecules, 
      affecting their ability to impede peptide aggregation. The study is of great 
      significance for the application and development of beta-carboline alkaloids against 
      T2DM.
CI  - (c) 2023 Wiley-VCH GmbH.
FAU - Wang, Yanan
AU  - Wang Y
AD  - Department of Chemistry, Renmin University of China, No.59, Zhong Guan Cun Street 
      Haidian District, Beijing, 100872, P. R. China.
FAU - Huo, Yan
AU  - Huo Y
AD  - Department of Chemistry, Renmin University of China, No.59, Zhong Guan Cun Street 
      Haidian District, Beijing, 100872, P. R. China.
FAU - Wang, Shao
AU  - Wang S
AD  - Department of Chemistry, Renmin University of China, No.59, Zhong Guan Cun Street 
      Haidian District, Beijing, 100872, P. R. China.
FAU - Zheng, Ting
AU  - Zheng T
AD  - Department of Chemistry, Renmin University of China, No.59, Zhong Guan Cun Street 
      Haidian District, Beijing, 100872, P. R. China.
FAU - Du, Weihong
AU  - Du W
AUID- ORCID: 0000-0002-9976-4515
AD  - Department of Chemistry, Renmin University of China, No.59, Zhong Guan Cun Street 
      Haidian District, Beijing, 100872, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230822
PL  - Germany
TA  - Chembiochem
JT  - Chembiochem : a European journal of chemical biology
JID - 100937360
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 94HMA1I78O (norharman)
RN  - 4FHH5G48T7 (Harmine)
RN  - 0 (Amyloid)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/metabolism/pathology
MH  - Islet Amyloid Polypeptide/chemistry
MH  - Harmine
MH  - Amyloid/chemistry
OTO - NOTNLM
OT  - aggregation
OT  - beta-carboline
OT  - hIAPP
OT  - inhibition
OT  - interactions
EDAT- 2023/07/24 06:42
MHDA- 2023/10/23 00:43
CRDT- 2023/07/24 05:00
PHST- 2023/07/18 00:00 [revised]
PHST- 2023/05/25 00:00 [received]
PHST- 2023/10/23 00:43 [medline]
PHST- 2023/07/24 06:42 [pubmed]
PHST- 2023/07/24 05:00 [entrez]
AID - 10.1002/cbic.202300395 [doi]
PST - ppublish
SO  - Chembiochem. 2023 Oct 17;24(20):e202300395. doi: 10.1002/cbic.202300395. Epub 
      2023 Aug 22.