PMID- 29954682
OWN - NLM
STAT- MEDLINE
DCOM- 20190131
LR  - 20210504
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 26
IP  - 14
DP  - 2018 Aug 7
TI  - Design, synthesis and biological evaluation of nitric oxide releasing derivatives 
      of dapagliflozin as potential anti-diabetic and anti-thrombotic agents.
PG  - 3947-3952
LID - S0968-0896(18)30938-6 [pii]
LID - 10.1016/j.bmc.2018.06.017 [doi]
AB  - The cardiovascular complications were highly prevalent in type 2 diabetes 
      mellitus (T2DM), even at the early stage of T2DM or the state of intensive 
      glycemic control. Therefore, there is an urgent need for the intervention of 
      cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and 
      SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and 
      anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2 
      inhibitory effects and anti-platelet aggregation activities, and its 
      anti-platelet effect mediated by NO was also confirmed in the presence of NO 
      scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and 
      excretion of urinary glucose during an oral glucose tolerance test in mice. 
      Potent and multifunctional hybrid, such as compound 2, is expected as a potential 
      candidate for the intervention of cardiovascular complications in T2DM.
CI  - Copyright (c) 2018. Published by Elsevier Ltd.
FAU - Li, Zheng
AU  - Li Z
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR 
      China.
FAU - Xu, Xue
AU  - Xu X
AD  - Guangzhou General Pharmaceutical Research Institute Co., Ltd., Guangzhou 510240, 
      PR China.
FAU - Deng, Liming
AU  - Deng L
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR 
      China.
FAU - Liao, Ruoxian
AU  - Liao R
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR 
      China.
FAU - Liang, Ruiying
AU  - Liang R
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR 
      China.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing 
      Medical University, 299 Qingyang Road, Wuxi, Jiangsu 214023, PR China. Electronic 
      address: zhangbo_cpu1713@163.com.
FAU - Zhang, Luyong
AU  - Zhang L
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR 
      China; Guangzhou Key Laboratory of Construction and Application of New Drug 
      Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, 
      PR China; Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical 
      University, Nanjing 210009, PR China. Electronic address: lyzhang@cpu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180614
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
SB  - IM
MH  - Adenosine Diphosphate
MH  - Animals
MH  - Benzhydryl Compounds/chemical synthesis/chemistry/*pharmacology
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - *Drug Design
MH  - Glucose Tolerance Test
MH  - Glucosides/chemical synthesis/chemistry/*pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoglycemic Agents/chemical synthesis/chemistry/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Molecular Structure
MH  - Nitric Oxide/*chemistry
MH  - Platelet Aggregation/drug effects
MH  - Rabbits
MH  - Structure-Activity Relationship
MH  - Venous Thrombosis/*drug therapy
OTO - NOTNLM
OT  - Cardiovascular complications
OT  - Diabetes
OT  - Hybrid
OT  - NO donor
OT  - SGLT2
EDAT- 2018/06/30 06:00
MHDA- 2019/02/01 06:00
CRDT- 2018/06/30 06:00
PHST- 2018/05/17 00:00 [received]
PHST- 2018/06/10 00:00 [revised]
PHST- 2018/06/13 00:00 [accepted]
PHST- 2018/06/30 06:00 [pubmed]
PHST- 2019/02/01 06:00 [medline]
PHST- 2018/06/30 06:00 [entrez]
AID - S0968-0896(18)30938-6 [pii]
AID - 10.1016/j.bmc.2018.06.017 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2018 Aug 7;26(14):3947-3952. doi: 10.1016/j.bmc.2018.06.017. 
      Epub 2018 Jun 14.