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Journal of Diabetology | Volume 3
Annual Summit on
Diabetes, Obesity & Heart
Diabetes, Endocrinology and Metabolic Syndrome
International Conference on
Joint Event
&
March 07-08, 2019 | London, UK
Computational approaches, including both indirect and direct
designshavebeenused inthesearchofnovel smallmolecules
as potential biologically active agents. The protein tyrosine
phosphatase1B (PTP1B) isbeenconsidered ispotential targets for
designing for antidiabetic agents as PTP1B inhibition results both
in increased insulin sensitivity and resistance to obesity, with no
abnormalities in growth or fertility or other pathogenetic effects.
Thus in search of small molecule as potential PTP1B inhibitors,
the indirect drug design approaches like CoMFA, CoMSIA and
pharmacophore modeling resulted in the design and synthesis
of a series of 2-[(4-methoxyphenyl) ethyl] acetamide derivatives
including a promising PTP1B inhibitor (IC50= 69µM) and another
series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols
where one compound showed 40.3% normalization of plasma
glucose levels at 100mg/kg in sugar-loadedmodel (SLM) and 32%
activity in streptozocin model (STZ). In continuation of this work
using computer assisted pharmacophore modeling and direct
drug design approaches like docking led to the identification and
synthesis of substituted sulfonamides and carboxamides where
the best compound of the sulfonamides and carboxamides
series showed very high activity with IC50 values 7.54 and 5.8µm
respectively. Both the compounds improved in vivo activity in
STZ model and restored the insulin level and the serum lipid
profile by significantly improving the insulin signaling and insulin
resistance. Altogether, both compounds present excellent profile
for development as candidate for future PTP1B targeted drug
discovery.
Speaker Biography
AnilKSaxena isactively involved inthedomainofmedicinalchemistry, includingCADD,drug
discovery and development research. He has more than 49 years of research experience
with 206 research publications, 24 reviews/articles in books and/monographs, 72 patents
and has delivered more than 180 invited lectures and chaired more than 48 sessions. He is
a Fellow of Royal Society of Chemistry, UK, Editorial Board Member of different prominent
journals like Medicinal Chemistry Research, SAR and QSAR in Environmental Research,
online International journal ARKIVOC and Patent Evaluator: Current Drugs, UK. He is also
series editor for book series “Topics in Medicinal Chemistry” published by Springer Verlag.
e:
Anil K Saxena
Central Drug Research Institute, India
Computational drug design in the search of protein tyrosine phosphatase 1B
inhibitors as potential antidiabetic agents