Dr. Sanghapal D. Sawant

Medical Chemistry Division
CSIR - Indian Institute of Integrative Medicine,Canal Road, Jammu – 180001
Email: sdsawant@iiim.ac.in

Positions Held  
Position Held Date Organization
Senior Scientist  2012 - Present CSIR-IIIM
Scientist 2009 - 2012 CSIR-IIIM
Scientist - B 2006 - 2009 CSIR-IIIM
Honours & Awards  
  • Recipient of the Expert in the Latvian Council of Science for Foreign Scientists, (Decision No. 32-2-2; 28th Nov 2012)
  • Inclusion of biography recognized by Marquis’s Who’s Who in World in 31st Edition 2014.
Membership  
  • Indian Science Congress Association
  • Asian Polymer Association

Research

Medicinal chemistry of natural product scaffolds for cancer drug discovery

In our cancer drug discovery program we are looking for isoform selective inhibitors of PI3K(α/β/γ/δ)/Akt-(1/2)/mTOR. The natural product scaffolds like liphagane is explored for its potential as selective PI3K inhibitor by medicinal chemistry approach. In vitro cell free and cell based screening of analogs is carried at intial stage, the active hits are identified. PK parameters, preformulation studies and physicochemical studies of NCEs of this scaffold are performed. The leads are being studied for their in vivo potential.

Apart from this, the distinct series of compounds based on purine quinazolinone, tri/tetrazolyl-quinazolinones, isatinyl quinazolinones, etc are also developed in one of the program. Where, selective PI3K hits have been identified and studied for detailed biological investigations.

Medicinal chemistry work Ecteinascidin (ET 743)

Discovery of next generation PDE-5 and PDE-4 inhibitors

Phosphodiesterase enzymes (PDE) are drruggable targets and many small molecules have been approved as drugs to treat different diseases ranging from erectile dysfunction (ED) to COPD. Sildenafil was being worked out by Pfizer in Nineties to treat COPD through inhibition of PDE isoform 4 and it turned out to be a good molecule to treat ED by inhibiting another isoform PDE5. Since then the race to find more potent and selective PDE5 inhibitors is going on in many laboratories. We have a program on discovery of novel small molecules based on pyrazolopyrimidinone scaffold. In some findings, few molecules have turned out to be more active than the sildenafil in enzyme based assays and also in vivo results corroborate with in vitro data. The PK profile and pre-formulation parameters also support for one of the lead identified for which the formulation studies are in progress.

Small molecule stem cell modulators from natural products origin: Target based approach

Targets:
(i) PI3K/Akt/mTOR
(ii) CDK-Gsk3β-Wnt/β-Catenin
(iii) Hedgehog
(iv) Notch
(v) EGFR
Various signaling pathways have been identified involved in controlling the fate of stem cells, such as Hedgehog, Wnt, Notch, PI3K/Akt, CDK etc. that direct differentiation of stem cells to different tissues or keep them undifferentiated and pluripotent. However, aberrant activation or attenuation of these pathways leads to the onset of several degenerative diseases and cancer. Natural products and designed small molecules targeting vital signaling pathways had shown the ability to reprogram lineage-committed cells and revert to more-primitive multipotent or pluripotent states. The target based strategy involving vital chemical scaffolds of natural origin are being exploited for its potential in this program.

Anti-microbials

Discovery of Nitrofuranyl-Pyrazolopyrimidine Bioisoteres and their activity against Staphylococcus aureus and Methicillin- and Vancomycin- Resistant Strains

Antitubercular (Discovery of Anti-TB agents)

Development of new synthetic methodologies

  • Metal-free synthetic methods
  • Oxone/TFA mediated reactions

a) C‒H oxygenation and N-trifluoroacylation of arylamines under metal free conditions: a convenient approach to 2-aminophenols and N-trifluoroacyl-ortho-aminophenols
b) Metal-Free Chemoselective ortho-C(sp2)–F Bond Hydroxylation and N-Trifluoroacylation of Fluoroarylamines for Domino Synthesis of 2-(N-Trifluoroacyl)aminophenols
c) Direct C–N bond cleavage of N-vinyl or N-allyl arylamines: a metal-free strategy for N-devinylation and N-deallylation
d) Applications of methods in drugs/drug intermediates or natural products

A Metal-Free Approach to Carboxylic Acids by Oxidation of Alkyl,  Aryl, or Heteroaryl Alkyl Ketones or Arylalkynes

  • K2S2O2 mediated reactions

A Greener Method for Transamidation of Amides with Amines in Aqueous Media under Metal-free Conditions

  • Iodine mediated reactions

DMSO/I2 mediated C‒C bond cleavage of α-ketoaldehydes followed by C‒O bond formation: A metal-free approach for one-pot esterification

Iodination catalyzed synthesis of diphenyl disulfide from aryla(sulfonyl)hydrazines

  • Organometallic reactions

Ligand and base-free synthesis of phenols by rapid oxidation of arylboronic acids using iron(III) oxide

Ligand free C–N bond formation in aqueous medium using a reusable Cu–Mn bimetallic catalyst

N-Heterocyclization of Hydrazines with M(acac)2-Complex in Aqueous Media for Pyrazole Synthesis under Microwave Conditions:  Applications in Late Stage Modifications

Publications

Click here for complete list.

  • Venkateswarlu, V.; Pathania, A. S.; Aravinda Kumar, K.A.; Mahajan, P.; Nargotra, A.; Vishwakarma, R. A.; Malik, F.A.; Sawant, S.D. 4-(N-phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines as Inhibitors of Mammalian Target of Rapamycin. Bioorganic & Medicinal Chemistry (2015), 23(15), 4237-4247.

  • Srinivas, M.; Hudwekar, A. D.; Venkateswarlu, V.; Reddy, G. L.; Aravinda Kumar, K. A.; Vishwakarma, R. A.; Sawant, S. D. A metal-free approach for transamidation of amides with amines in aqueous media. Tetrahedron Letters, 2015, 56(33), 4775–4779.

  • Venkateswarlu, V.; Aravinda Kumar, K. A.; Gupta, S.; Singh, D.; Vishwakarma R.;. Sawant, S. D. DMSO/I2 mediated C‒C bond cleavage of α-ketoaldehydes followed by C‒O bond formation: A metal-free approach for one-pot esterification. Organic and Biomolecular Chemistry (2015), 13, 7973-7978.

  • Kumar, K. A. A.; Venkateswarlu, V.; Vishwakarma, R. A.; Sawant, S. D. A metal-free approach to carboxylic acids by oxidation of alkyl, aryl or heteroaryl alkyl ketones and arylalkynes. Synthesis (2015), DOI: 10.1055/s-0034-1381026.

  • Balgotra, S.; Venkateswarlu, V.; Vishwakarma, R. A.; Sawant, S. D. Direct C‒N bond cleavage of N-vinyl or N-allyl arylamines: A metal-free strategy for N-devinylation and N-deallylation, Tetrahedron Letters 2015, 56, 4289–4292.

  • Raghupathy, R.; Ambika, A.; Polley, A.; Singh, P. P.; Yadav, M.; Johnson, C.; Suryawanshi, S.; Saikam, V.; Sawant, S. D.; Panda, A.; Guo, Z.; Vishwakarma, R. A.; Rao, M.; Mayor, S. Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins. Cell (2015), 161(3), 581-594.

  • Guru, S. K.; Venkateswarlu, V.; Malik, F. A.; Vishwakarma, R. A.; Sawant, S. D.; Bhushan, S. A novel quinoline based second-generation mTOR inhibitor that induces apoptosis and disrupts PI3K-Akt-mTOR signaling in human leukemia HL-60 cells, Anti-Cancer Agents in Medicinal Chemistry (2015), DOI:10.2174/1871520615666150402093558

  • Venkateswarlu, V.; Balgotra, S.; Vishwakarma, R. A.; Sawant, S. D. Metal-free Chemoselective ortho-C(sp2)–F Bond Hydroxylation and N-trifluoroacylation of Fluoroarylamines for Domino Synthesis of N-trifluoroacyl-ortho-aminophenols. Synlett, (2015), 26, 1258–1262.

  • Sawant, S.D.; Reddy, G.L.; Dar, I.M.; Srinivas, M.; Gupta, G.; Sahu, P.K.; Mahajan, P.; Singh, S.; Sharma, S.C.; Tikoo, M.; Singh, G.D.; Nargotra, A.; Vishwakarma, R.A.; Syed, S.H. Discovery of Novel Pyrazolopyrimidinone Analogs as Potent Inhibitors of Phosphodiesterase Type-5. Bioorganic & Medicinal Chemistry (2015), 23(9), 2121-2128.

  • Mungala, G.; Reddy Yempala, K.; Singh, S.; Sharma, S.; Kalia, N.P.; Singh, V.K.;  Kumar, S.; Sawant, S. D.; Khan, I. A.; Vishwakarma, R.A.; Singh, P.P. Synthesis of new generation triazolyl and isoxazolyl containing 6-nitro-2,3-dihydroimidazooxazoles as anti-TB agents: In vitro, Structure-activity relationship, pharmacokinetics and in vivo evaluation Organic and Biomolecular Chemistry (2015), 13, 3610-3624.

  • Reddy, G. L.; Guru, S. K.; Srinivas, M.; Pathania, A.S.; Mahajan, P.; Nargotra, A.; Bhushan, S.; Vishwakarma, R. A.; Sawant, S. D. Synthesis of 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one analogs and their biological evaluation as anticancer agents: mTOR inhibitors. European Journal of Medicinal Chemistry (2014), 10(80), 201-208.

  • Venkateswarlu, V.; Aravinda Kumar, K. A.; Balgotra, S.; Reddy, G. L.; Srinivas, M.; Vishwakarma, R. A.;  Sawant, S. D.  C‒H Oxygenation and N-Trifluoroacylation of Arylamines Under Metal-Free Conditions: A Convenient Approach to 2-Aminophenols and N-Trifluoroacyl-ortho-aminophenols. Chemistry: A European Journal (2014), 20(22),  6641–6645.

  • Yadav, M.; Raghupathy, R.; Saikam, V.; Dara, S.; Singh, P.P.; Sawant, S. D.; Mayor, S.; Vishwakarma, R. A.; Synthesis of non-hydrolysable mimics of glycosylphosphatidylinositol (GPI) anchors. Organic and Biomolecular Chemistry (2014), 12, 1163.

  • Sawant, S. D.; Hudwekar, A. D.; Aravinda Kumar, K. A.; Venkateswarlu, V.; Singh, P.P.; Vishwakarma, R. A. Ligand- and base-free synthesis of phenols by rapid oxidation of arylboronic acids using iron(III) oxide; Tetrahedron Letters (2014), 55, 811-814. (Article selected by the Editorial Board of SYNFACTS for its important insights; Oxidation of ArB(OH)2 using Fe2O3 under solar VIS-light irradiation, Synfacts2014; 10(4): 0445. DOI: 10.1055/s-0033-1340906).

  • Bharate, S.B.; Sawant, S.D.; Singh, P.P.; Vishwakarma, R.A.; Kinase Inhibitors from Marine Origin. Chemical Review (2013), 113(8), 6761–6815.

Patents:

  • Kumar, H.M.S.; Sawant, S.D.; Qazi, N.A.; Singh, S.K.; Verma, M.; Saxena, A.K.; Sethi, V.K.; Taneja, S.C.; Qazi, G.N. Spiro-derivatives of parthenin as novel anticancer agents (US 2011/0201661 A1; EP2265620 A1; WO/2009/110007.)

  • Sampath Kumar, H.M.; Sawant, S.D.; Reddy, D.M.; Banday, A.H.; Qazi, G.N. Novel hybrids of perfumery molecules with extremolytes, humectants and exfoliating agents for the development of new generation multiple action skin/beauty care bio-conjugates; (0656DEL2009; 785/DEL/2010 A; 786/DEL/2010 A; 787/DEL/2010 A.

  • Vishwakarma, R.A.; Sawant S.D.; Singh P.P.; Dar A.H.; Sharma P.R.; Saxena A.K.; Nargotra A.; Aravind Kumar K.A.; Ramesh, M.; Qazi A.K.; Hussain A.; Chanauria N. Boronic acid bearing liphagane compounds as PI3K-alpha/beta inhibitors. (WO 2013/140147 A1)

  • Singh, P.P.; Munagala G.; Reddy Yempala, K.; Khan, I.A.; Kalia, N.P.; Singh Rajput, V.; Nargotra, A.; Sawant, S.D.; Vishwakarma, R.A. 6-Nitro-2,3-dihydroimidazo[2,1-b]oxazoles and process for the preparation thereof. (WO2015/049693A1, 04/2015)

  • Sawant, S.D.; Reddy, G.L.; Srinivas, M.; Hussain, S.S.; Dar, M.I.; Nargotra, A.; Mahajan, P.; Vishwakarma, R.A. Novel Pyrazolopyrimidinones for the treatment of impotence and process for the preparation thereof. (NF No. : 0281DEL2014)

Current Students

Our group is engaged in research on discovery of new molecules using a target based approach, which have established the clinical proof of concept. Design and synthesis of novel molecules is primarily based on natural product scaffolds or on the basis of molecules being currently investigated in clinical stages/approved drugs. The therapeutic areas covered under discovery program includes cancer, antimicrobials and discovery of novel PDE-5 and/or 4 inhibitors for the treatment of MED and/or COPD and other applications.

Student
Fellowship
Research Theme

Lakshma Reddy G.
glreddy09@gmail.com

Senior Research Fellow (CSIR)
Pyrazolopyrimidinones as selective PDE5 inhibitors

Maheshuni Srinivas
vasiiim007@gmail.com

Senior Research Fellow (CSIR)

Novel quinazolinones as selective PI3K-δ inhibitors

Aravinda Kumar
anjaneya.kolluru@gmail.com

Senior Research Fellow (UGC/CSIR)

Medicinal chemistry of liphagane scaffold

V. Venkateswarlu
vunnam.choudhary@yahoo.com

Senior Research Fellow (UGC/CSIR)

Design and synthesis of quinoline based mTOR and Akt inhibitors

Abhinandan D. Hudwekar
abhinandanh14@gmail.com

Senior Project Fellow

Design and synthesis of PDE5 and PDE4 inhibitors

Shilpi Balgotra
shilpibalgotra@gmail.com

Project Fellow

Metal-free strategies for new synthetic methods: Applications in medicinal chemistry

Sorav Gupta
sourabh.gupta789@gmail.com

Junior Research Fellow (UGC)

Applications of synthetic methods in medicinal chemistry and drug discovery