Department of Chemistry

Xavier University of Louisiana

Jayalakshmi Sridhar
Assistant Professor

Telephone Number: 504-520-7519
Room Number: NCF Annex- Room 323
Email Address: jsridhar@xula.edu
Courses

Organic Chemistry Lecture, Drill, and Laboratory (CHEM 2210, 2210D, 2220, 2220D, 2230L, 2240L and 4320) and Drug Design Using Computational Chemistry (CHEM 4153)

Short Professional Biography

2012-present, Assistant Professor of Chemistry
2009-2012, Research Associate, Xavier University of Louisiana, New Orleans, LA, USA.
2005-2008, Visiting Researcher, Department of Bioengineering, University of California, Riverside, CA, USA
2002-2005, Postdoctoral position, Department of Neurosciences and Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
1999-2001, Research Associate, Indian Institute of Technology, Chennai, India.
1998- Ph.D., Indian Institute of Chemical Technology, Osmania University, India.

Research Interest

Drug Discovery using Organic Synthesis based on Molecular Modeling
We are presently involved in two major areas of research, namely, development of modulators of protein kinases, liver X receptors and cytochrome P450 enzymes for cancer therapy, Alzheimers disease, atherosclerosis and angiogenesis. We analyze computationally different aspects of protein-drug interactions to understand the drug potency and specificity. We use molecular modeling and computational methods for structure based drug design, quantitative structure activity relationships (QSAR) of biologically active compounds, homology modeling of proteins and molecular dynamic studies. Organic synthetic methods are used to synthesize the designed inhibitors.

When cell life cycle is not regulated, the cell continuously divides out of control leading to the formation of cancer. Nearly all aspects of cell life are controlled by the reversible phosphorylation of proteins which are mainly regulated by protein kinases. There are 518 human protein kinases. HER2D16 is an oncogenic isoform of the HER2 protein that is overexpressed in ~30% of breast cancer patients that is known to enhance transformation activity over wild-type HER2, leading to node-positive breast cancer and trastuzumab resistance. Our group has identified new inhibitors for the HER2D16 overexpressed breast cancer cells. Our group also works on the development of small molecule inhibitors for protein kinases (Cyclin Dependent Kinase, CDK; Pim1 kinase, Casein Kinase 1 delta) that can target specific disease conditions such as breast & prostate cancer, Alzheimers disease, etc. Achieving good potency and selectivity profile for these potential drug candidates is the goal of this project.

Liver X receptors are nuclear receptors that act as oxysterol sensors, regulating genes involved in cholesterol and lipid metabolism. Our laboratory is focused on the development of new activators/antagonists of LXRa and LXRb as therapeutics for atherosclerosis and cancer. Cytochrome P450 enzymes metabolize exogenous and endogenous compounds including pro-carcinogens and poly aromatic hydrocarbons through oxidation. The inhibition of these enzymes should help in preventing many of the cancers caused by environmental pollutants. Our efforts are directed towards the design and development of molecules that can act as mechanism based inhibitors of the cytochrome P450 enzymes.

Current Grant Support

1) Louisiana Biomedical Research Network (LBRN)
Title: Development of Casein Kinase 1 Inhibitors as Therapeutics for Alzheimer’s Disease
May 1, 2015 to April 30, 2018
Role: PI;  Amount: $ 300,000

2) National Institutes of Health, R15
Title: Generation of Liver X Receptor Agonists with LXRb Subtype Selectivity using Modern Computational and Chemical Synthetic Methods
Jan 1, 2015 to Dec 31, 2017
Role: Co-PI;  Amount: $339,391.

Recent Publications
  1. Identification of quinones as novel PIM1 kinase inhibitors. Schroeder RL, Goyal N, Bratton M, Townley I, Pham N, Tram P, Stone T, Geathers J, Nguyen K, Sridhar J. Bioorg Med Chem Lett. 2016 Jul 1; 26(13): 3187-91.
  2. Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome P450 inhibition: a patent evaluation WO2015048311 (A1). Schroeder RL, Tram P, Liu J, Foroozesh M, Sridhar J. Expert Opin Ther Pat. 2015 Oct 29:1-9.
  3. Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in Aggressive Metastatic Breast Cancer. Schroeder, R. L., Stevens, C. K. and Sridhar J. Molecules. 2014 Sep 23;19(9):15196-212.
  4. Identification of quinones as HER2 inhibitors for the treatment of trastuzumab resistant breast cancer. Sridhar J, Sfondouris ME, Bratton MR, Nguyen TL, Townley I, Klein Stevens CL, Jones FE. Bioorg Med Chem Lett., 2014 Jan 1;24(1):126-31. doi: 10.1016/j.bmcl.2013.11.064. Epub 2013 Dec 3.
  5. Modification and Biological Evaluation of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion. Zheng, S; Zhong, Q; Xi, Y; Schroeder, R; Sridhar, J; Mottamal, M; Zhang, Q; He, L; McFerrin, H; Wang*, G., J. Med. Chem., 2014 Aug 14;57(15):6653-67.
  6. Ethynylflavones, Highly Potent and Selective Inhibitors of Cytochrome P450 1A1. Goyal, N; Liu, J; Lovings, L; Dupart, P; Taylor, S; Bellow, S; Mensah, L; McClain, E; Dotson, B; Sridhar, J; Zhang, X; Zhao, M; Foroozesh, M. Chem. Res. Toxicol., 2014 Aug 18;27(8):1431-9.
  7. Cytochrome P450 family 1 inhibitors and structure-activity relationships. Liu J, Sridhar J, Foroozesh M. Molecules, 2013 Nov 25; 18(12):14470-95. doi: 10.3390/molecules181214470.
  8. Pyranoflavones: a group of small-molecule probes for exploring the active site cavities of cytochrome P450 enzymes 1A1, 1A2, and 1B1. Liu J, Taylor SF, Dupart PS, Arnold CL, Sridhar J, Jiang Q, Wang Y, Skripnikova EV, Zhao M, Foroozesh M. J Med Chem., 2013 May 23; 56(10):4082-92. doi: 10.1021/jm4003654. Epub 2013 May 2.
  9. Insights on cytochrome P450 enzymes and inhibitors obtained through QSAR studies. Sridhar J, Liu J, Foroozesh M, Stevens CL. Molecules, 2012, 17(8), 9283-305.
  10.  Inhibition of Cytochrome P450 Enzymes by Quinones and Anthraquinones. Sridhar J, Foroozesh M, Stevens CL. Chem Res Toxicol., 2012, 25(2), 357-65.
  11. QSAR Models of Cytochrome P450 Enzyme 1A2 Inhibitors using CoMFA, CoMSIA and HQSAR. Sridhar J, Foroozesh M, Stevens CL. SAR and QSAR in Environmental Research, 2011, 1-17, published online on October 17, 2011.
  12. Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells. Jiang Q, Payton-Stewart F, Elliott S, Driver J, Rhodes LV, Zhang Q, Zheng S, Bhatnagar D, Boue SM, Collins-Burow BM, Sridhar J, Stevens C, McLachlan JA, Wiese TE, Burow ME, Wang G. J Med Chem., 2010, 53(16),6153-63.
  13. In Silico Studies of Polyaromatic Hydrocarbon Inhibitors of Cytochrome P450 Enzymes 1A1, 1A2, 2A6, and 2B1. Sridhar J, Jin P, Liu J, Foroozesh M, Stevens CL. Chem. Res. Toxicol., 2010, 23(3), 600-7.
  14. Selectivity and Potency of Cyclin-Dependent Kinase Inhibitors. Sridhar, J., Akula, N., Pattabiraman, N. Am. Assoc. Pharm. Sci. J., 2006, 8(1),E204-21.
  15. CDK inhibitors as anti-cancer agents: Perspectives for the future. Authors: Sridhar, J., Pattabiraman, N., Rosen, E. M., Pestell, R. G. Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents, Edited by Paul James Smith, Eddy W. Yue. CRC Press, 2006, Pg. 389-402.
  16. Mapping the Similarities/Dissimilarities of the active sites of CDK2 and CDK4. Akula, N. Sridhar J, Pattabiraman, N. Hoya Technical Research Bulletin, 2004, 1, 5-7.
  17. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease. Kozikowski A. P., Gaisina IN, Petukhov P. A., Sridhar J, King LT, Blond SY, Duka T, Rusnak M, Sidhu A., ChemMedChem., 2006, 1(2), 256-66.
  18. Identification of novel angiogenesis inhibitors. Sridhar J, Akula, N., Sivanesan, D., Narasimhan, M., Rathinavelu, A., Pattabiraman N., Bioorg. Med. Chem. Lett. 2005, 15(18), 4125-9.
  19. Binding modes of 6,7 di-substituted 4-anilinoquinoline-3-carbonitriles to EGFR. Akula, N., Bhalla, J., Sridhar J, Pattabiraman, N., Bioorg. Med. Chem. Lett. 2004, 14(13), 3397-400.
  20. New Bivalent PKC Ligands Linked By A Carbon Spacer: Enhancement In Binding Affinity; Sridhar J, Wei Z-L, Nowak I, Lewin N. E., Ayres, J. A., Pearce, L. V., Blumberg, P. M., Kozikowski, A. P., J. Med. Chem. 2003, 46(19), 4196-204.
  21. Synthesis and isozyme selectivity of small molecule protein kinase C inhibitors: a review of patents.Sridhar, J, Pattabiraman, N. Exp. Opin. Ther. Patents 2005, 15(12), 1691-1701.

Reviews

  1. Selectivity and Potency of Cyclin-Dependent Kinase Inhibitors. Jayalakshmi Sridhar, Akula, N., Pattabiraman, N. Am. Assoc. Pharm. Sci. J., 2006, 8(1), E204-21.
  2. Synthesis and isozyme selectivity of small molecule protein kinase C inhibitors: a review of patents. Jayalakshmi Sridhar, Pattabiraman, N. Exp. Opin. Ther. Patents 2005, 15(12), 1691-1701.

Patents

  1. Vascular Endothelial Receptor Specific Small Molecule Inhibitors. Rathinavelu, A., Pattabiraman, N., Jayalakshmi Sridhar, Dakshanamurthy, S. Publication No: US2007249575 – Date: 2007-10-25
  2. Inhibitors of Glycogen Synthase Kinase 3. Kozikowski AP, Gaisina IN, Petukhov PA, Jayalakshmi Sridhar, Tueckmantel W. Publication No: WO2007008514 - Date: 2007-01-18.

Book Chapter

  1. CDK inhibitors as anti-cancer agents: Perspectives for the future. Authors: Jayalakshmi Sridhar, Nagarajan Pattabiraman, Eliot M. Rosen, Richard G. Pestell. Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents, Edited by Paul James Smith, Eddy W. Yue. CRC Press, 2006, Pg. 389-402.

Department of Chemistry

504-520-5082