Dr Kovela Satish, PhD - Indian Institute of Chemical Technology, Hyderabad

Dr Kovela Satish

PhD

Indian Institute of Chemical Technology, Hyderabad

Hyderabad, Telangana | India

Main Specialties: Chemistry

Additional Specialties: Synthetic and medicinal chemistry

Dr Kovela Satish, PhD - Indian Institute of Chemical Technology, Hyderabad

Dr Kovela Satish

PhD

Introduction

Primary Affiliation: Indian Institute of Chemical Technology, Hyderabad - Hyderabad, Telangana , India

Specialties:

Additional Specialties:

Education

Aug 2015
Indian Institute of Chemical Technology, Hyderabad
PhD
Synthetic Organic Chemistry

Experience

Apr 2016
Postdoc
Purdue University
West Lafayette, USA
Sep 2015
Associate Scientist
GVK Bioscience
Nacharam, Hyderabad

Publications

13Publications

126Reads

94Profile Views

1PubMed Central Citations

Asymmetric Diels–Alder reaction of 3-(acyloxy) acryloyl oxazolidinones: optically active synthesis of a high-affinity ligand for potent HIV-1 protease inhibitors

RSC Adv., 2019, 9, 41755–41763

RSC Advances

We describe here our investigation of the asymmetric Diels–Alder reaction of chiral 3-(acyloxy)acryloyl

oxazolidinones as dienophiles in various Lewis-acid promoted reactions with cyclopentadiene. The

resulting highly functionalized cycloadducts are useful intermediates for the synthesis, particularly for the

optically active synthesis of 6-5-5 tricyclic hexahydro-4H-3,5-methanofuro[2,3-b]pyranol (3) with five

contiguous chiral centers. This stereochemically defined crown-like heterocyclic derivative is an

important high affinity ligand for a variety of highly potent HIV-1 protease inhibitors. Among the various

dienophiles and Lewis acid-mediated reactions surveyed, 3-(4-methoxybenzoyl)acryloyl oxazolidinone

as the dienophile and diethylaluminum chloride as the Lewis-acid provided the desired endo product

with excellent diastereoselectivity. The cycloaddition was carried out in multi-gram scale and the

cycloadduct was efficiently converted to alcohol 3 with high enantiomeric purity. The optically active

ligand was then transformed into potent HIV-1 protease inhibitor 2.

View Article
December 2019

Impact Factor 3.049

1 Read

Potent HIV-1 Protease Inhibitors Containing Carboxylic and Boronic Acids: Effect on Enzyme Inhibition and Antiviral Activity and Protein-ligand X-ray Structural Studies

10.1002/cmdc.201900508

ChemMedChem

We report here the synthesis and biological evaluation of
phenylcarboxylic acid and phenylboronic acid containing HIV-1 protease
inhibitors and their functional effect on enzyme inhibition and antiviral
activity in MT-2 cell lines. Inhibitors bearing bis-THF ligand as P2 ligand
and phenylcarboxylic acids and carboxamide as the P2' ligands, showed
very potent HIV-1 protease inhibitory activity. However, carboxylic acid
containing inhibitors showed very poor antiviral activity compared to
carboxamide-derived inhibitors which showed good antiviral IC50 value.
Boronic acid-derived inhibitor with bis-THF as the P2 ligand showed very
potent enzyme inhibitory activity, but it showed relatively reduced antiviral
activity compared to darunavir in the same assay. Boronic acidcontaining
inhibitor with a P2-Crn-THF ligand also showed potent
enzyme Ki but significantly reduced antiviral activity. We have evaluated
antiviral activity against a panel of highly drug-resistant HIV-1 variants.
One of the inhibitors maintained good antiviral activity against HIVDRVRP20
and HIVDRVRP30 viruses. We have determined high resolution X-ray
structures of two synthetic inhibitors bound to HIV-1 protease and
obtained molecular insight into the ligand-binding site interactions.

View Article
October 2019

Impact Factor 3.009

2 Reads

Potent HIV-1 protease inhibitors incorporating squaramide-derived P2 ligands: Design, synthesis, and biological evaluation.

Bioorg Med Chem Lett 2019 Sep 5;29(18):2565-2570. Epub 2019 Aug 5.

Department of Refractory Viral Infections, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch National Cancer Institute, Bethesda, MD 20892, USA; Division of Clinical Sciences, Kumamoto University Hospital, Kumamoto 860-8556, Japan.

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http://dx.doi.org/10.1016/j.bmcl.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711809PMC
September 2019
2.420 Impact Factor

Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.

Eur J Med Chem 2018 Dec 18;160:171-182. Epub 2018 Sep 18.

Department of Refractory Viral Infections, National Center for Global Health & Medicine Research Institute, Tokyo, 162-8655, Japan; Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, 860-8556, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.

We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.

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https://linkinghub.elsevier.com/retrieve/pii/S02235234183081
Publisher Site
http://dx.doi.org/10.1016/j.ejmech.2018.09.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237192PMC
December 2018
32 Reads
4.816 Impact Factor

Enantioselective Synthesis of a Cyclopropane Derivative of Spliceostatin A and Evaluation of Bioactivity.

Org Lett 2018 11 5;20(22):7293-7297. Epub 2018 Nov 5.

Department of Molecular Cell and Developmental Biology and Center for Molecular Biology of RNA , University of California , Santa Cruz , California 95064 , United States.

Spliceostatin A is a potent inhibitor of spliceosomes and exhibits excellent anticancer activity against multiple human cancer cell lines. We describe here the design and synthesis of a stable cyclopropane derivative of spliceostatin A. The synthesis involved a cross-metathesis or a Suzuki cross-coupling reaction as the key step. The functionalized epoxy alcohol ring was constructed from commercially available optically active tri- O-acetyl-d-glucal. The biological properties of the cyclopropyl derivative revealed that it is active in human cells and inhibits splicing in vitro comparable to spliceostatin A.

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http://pubs.acs.org/doi/10.1021/acs.orglett.8b03228
Publisher Site
http://dx.doi.org/10.1021/acs.orglett.8b03228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519444PMC
November 2018
9 Reads
6.500 Impact Factor

Design and Synthesis of Highly Potent HIV-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems as Novel P2 Ligands: Structure-Activity Studies, Biological and X-ray Structural Analysis.

J Med Chem 2018 05 15;61(10):4561-4577. Epub 2018 May 15.

Departments of Infectious Diseases and Hematology , Kumamoto University Graduate School of Biomedical Sciences , Kumamoto 860-8556 , Japan.

The design, synthesis, and biological evaluation of a new class of HIV-1 protease inhibitors containing stereochemically defined fused tricyclic polyethers as the P2 ligands and a variety of sulfonamide derivatives as the P2' ligands are described. A number of ring sizes and various substituent effects were investigated to enhance the ligand-backbone interactions in the protease active site. Inhibitors 5c and 5d containing this unprecedented fused 6-5-5 ring system as the P2 ligand, an aminobenzothiazole as the P2' ligand, and a difluorophenylmethyl as the P1 ligand exhibited exceptional enzyme inhibitory potency and maintained excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The umbrella-like P2 ligand for these inhibitors has been synthesized efficiently in an optically active form using a Pauson-Khand cyclization reaction as the key step. The racemic alcohols were resolved efficiently using a lipase catalyzed enzymatic resolution. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.

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http://dx.doi.org/10.1021/acs.jmedchem.8b00298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044451PMC
May 2018
18 Reads
6.253 Impact Factor

Design of Highly Potent, Dual-Acting and Central-Nervous-System-Penetrating HIV-1 Protease Inhibitors with Excellent Potency against Multidrug-Resistant HIV-1 Variants.

ChemMedChem 2018 04 15;13(8):803-815. Epub 2018 Mar 15.

Departments of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan.

Herein we report the design, synthesis, X-ray structural, and biological studies of an exceptionally potent HIV-1 protease inhibitor, compound 5 ((3S,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl ((2S,3R)-4-((2-(cyclopropylamino)-N-isobutylbenzo[d]thiazole)-6-sulfonamido)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)carbamate). Using structure-based design, we incorporated an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran as the P2-ligand, a cyclopropylaminobenzothiazole as the P2'-ligand, and a 3,5-difluorophenylmethyl group as the P1-ligand. The resulting inhibitor 5 exhibited exceptional HIV-1 protease inhibitory and antiviral potency at the picomolar level. Furthermore, it displayed antiviral IC values in the picomolar range against a wide panel of highly multidrug-resistant HIV-1 variants. The inhibitor shows an extremely high genetic barrier against the emergence of drug-resistant variants. It also showed extremely potent inhibitory activity toward dimerization as well as favorable central nervous system penetration. We determined a high-resolution X-ray crystal structure of the complex between inhibitor 5 and HIV-1 protease, which provides molecular insight into the unprecedented activity profiles observed.

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http://dx.doi.org/10.1002/cmdc.201700824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912973PMC
April 2018
19 Reads
3.009 Impact Factor

Nazarov cyclization of divinyl and arylvinyl epoxides: application in the synthesis of resveratrol-based natural products.

Chemistry 2015 Apr 11;21(17):6475-80. Epub 2015 Mar 11.

Division of CPC (Organic Chemistry-II), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad-500007 (India).

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http://doi.wiley.com/10.1002/chem.201500362
Publisher Site
http://dx.doi.org/10.1002/chem.201500362DOI Listing
April 2015
15 Reads
1 Citation
5.731 Impact Factor

Total synthesis and absolute configuration of curvularides A-E.

J Org Chem 2012 Nov 8;77(22):10010-20. Epub 2012 Nov 8.

Division of Crop Protection Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.

The first total synthesis of curvularides A-E, isolated from a culture broth of the endophytic fungus Curvularia geniculata, is described. The divergent total synthesis reported herein confirmed the absolute configurations of curvularides A-E and supported that these natural products might be obtained from a common biosynthetic pathway. The key steps involved in the synthesis were the diastereoselective hydrogenation of exo-methylene-?-butyrolactone to ?-methyl-?-butyrolactone, Sharpless kinetic resolution, Sharpless asymmetric epoxidations, and intramolecular and intermolecular epoxide openings.

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http://dx.doi.org/10.1021/jo301264kDOI Listing
November 2012
26 Reads
4.805 Impact Factor

Cytotoxic diterpenoid quinonemethides from the roots of Pygmacopremna herbacea

Bioorganic & Medicinal Chemistry Letters 21 (2011) 4581–4584

Two new diterpenoid quinonemethides (1 and 2) along with two known compounds (3 and 4) were isolated from the hexane and ethyl acetate extracts of root nodules of Pygmacopremna herbacea. The structures of the new compounds were established by spectroscopic data interpretation. Single crystal X-ray diffraction analysis confirmed the structure of 1. The cytotoxic activities of these compounds were evaluated against A 549, HEPG2, MCF-7, PC-3 and HELA cancer cell lines. Compounds 4, 2 and 1 were shown very good cytotoxic activity.

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November -0001

Impact Factor 2.442

14 Reads

Two new diterpenoids from the roots of Pygmacopremna herbacea

Phytochemistry Letters 12 (2015) 129–132

Two new diterpenoids, neobharangi-d-lactone (1) and bharangi quinone (2) along with two known compounds neobharangin (3) and bharangin (4) were isolated from the ethyl acetate extract of root nodules of Pygmacopremna herbacea. The structures of the new compounds were established by 1D and 2D NMR spectroscopic data.

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November -0001

Impact Factor 1.575

13 Reads

Two new diterpenoids from the root nodules of Pygmacopremna herbacea (Roxb.) Moldenke

Phytochemistry Letters 4 (2011) 109–112

Bharangin (1) analogues, bharangi-g-lactone (2) and bharangi-d-lactone (3) were isolated from the ethyl acetate extract of the root nodules of the indigenous medicinal plant Pygmacopremna herbacea (Roxb.) Moldenke (Gantubharangi). Compound 3 was also prepared from bharangin by treating with 2 N KOH in methanol at room temperature. The structures of the compounds were established by means of spectral data analysis, including high field 2D NMR studies.

View Article
November -0001

Impact Factor 1.575

16 Reads

Top co-authors

Arun K Ghosh
Arun K Ghosh

Purdue University

6
Satish Kovela
Satish Kovela

Purdue University

6
Hiroaki Mitsuya
Hiroaki Mitsuya

National Cancer Institute

4
Manabu Aoki
Manabu Aoki

Jikei University School of Medicine

3
Yuan-Fang Wang
Yuan-Fang Wang

Georgia State University

3
Johnson Agniswamy
Johnson Agniswamy

Georgia State University

3
Margherita Brindisi
Margherita Brindisi

University of Siena

3
Irene T Weber
Irene T Weber

Georgia State University

3
Bhavanam Sekhara Reddy
Bhavanam Sekhara Reddy

University of Hyderabad

2