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Volume 8 Medicinal Chemistry
ISSN: 2161-0444 Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10th World Congress on
Medicinal Chemistry and Drug Design
Pyrazoline containingmalonyl CoAdecarboxylase inhibitors: Design, synthesis and in vitro evaluation
C S Ramaa and Deepali M Jagdale
Bharati Vidyapeeth’s College of Pharmacy, India
Introduction: Cardiovascular disease is one of the leading causes of death in the modern world. Impaired cardiac efficiency
is an important contributor to the severity of cardiovascular disease. Impaired cardiac efficiency is caused by an inadequate
supply of oxygen to the heart. Malonyl-CoA decarboxylase (MCD) decarboxylates malonyl-CoA to acetyl-CoA. Therefore,
the inhibition of MCD increases the level of malonyl-CoA, which further reduces fatty acid oxidation and increases glucose
oxidation in the mitochondria. A shift in the mitochondrial metabolism from fatty acid to glucose oxidation increases
Adenosine tri phosphate production. Thus, the heart may receive more energy even if the oxygen supply is less. In addition,
increased glucose oxidation reduces pyruvate in cellular fluids, improving the pH balance of heart cells. Recently, researchers
have synthesized MCD inhibitors based on this novel approach of increasing energy supply to the heart.
In the present work series of small molecules (5a–5m, 6a–6j) were schematically designed and synthesized using simple chemical
procedures. Their structures were confirmed based upon findings from infrared, 1H nuclear magnetic resonance (NMR), 13C
NMR, and mass spectra. The derivatives were evaluated for their in vitro malonyl CoA decarboxylase inhibition activity by
using fluorimetric assay. Pyrazol-1-yl-1, 3-thaizol-4(5H)-one derivative (5a–5m) showed better activity than pyrazol-1- yl-1-
ethanone derivatives (6a–6j). Compounds 5e, 5j, and 6f showed an excellent in vitro malonyl CoA decarboxylase inhibition
activity with IC50 value 0.10, 0.27, and 0.26 μM, respectively. These most active compounds 5e, 5j, and 6f were docked into
malonyl-CoA decarboxylase (HsMCD, PDB ID: 2YGW) to study ligand–protein interaction.
Biography
C S Ramaa is a Professor and Head of Department of Pharmaceutical Chemistry at Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai. She received her PhD in
Pharmaceutical Chemistry from University Department of Chemical Technology. She has been working at Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai. She
has received several grants from renowned funding agencies like Department of Science and Technology, Basic Research in Nuclear Sciences, Lady Tata Memorial Trust
and University of Mumbai. She has published more than 35 research and review articles in international and national esteemed journals. She has also presented more than
30 presentations at national and international conferences. She has been awarded as Best Research Guide for national level PharmInnova Award.
C S Ramaa et al., Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-039