Sadanandan Velu, Assistant Professor of Chemistry, obtained his MS degree at the University of Calicut, India (1985) and obtained his Ph.D. degree in Organic Chemistry at the University of Madras, India (1993). He did his postdoctoral research at the University of Alabama and at Clemson University. Dr. Velu joined the medicinal chemistry division of the Center for Biophysical Sciences and Engineering (CBSE) of UAB in 1997 and worked as a staff scientist till 2004. He also held a joined appointment in the UAB Department of chemistry as a research faculty during 2002-2004. Dr. Velu became an Assistant Professor at the Department of Chemistry in August 2004.

Office: CHEM 280
Telephone: 205.975.2478
FAX: 205.934.2543
E-mail: svelu@uab.edu

Research Interests

The main focus of this laboratory is drug discovery and development. The students who work on these projects will be trained in organic synthesis, spectroscopy, molecular modeling, in-silico virtual screening, lead identification, structure activity relationship studies, lead optimization, in vitro enzyme kinetic assays and cell based assays. The ongoing projects are listed below.

Anticancer Drug Discovery

The past decade has witnessed an immense increase in the development and clinical use of potent anticancer agents with novel structures. Many of these drugs function by interacting with DNA and more specifically by modulating the activities of the nuclear enzymes such as topoisomerase I and topoisomerase II. These enzymes are responsible for generating necessary topological and conformational changes in DNA and are critical to many cellular processes such as replication and transcription. Topoisomerases have been classified into type I and II based on their ability to produce transient protein mediated single strand or double strand breaks. Topoisomerase inhibitors interfere with the breaking and rejoining reactions of these enzymes by trapping an abortive enzyme-DNA cleavable complex. Such inhibition of mammalian topoisomerases has been recognized as an effective approach for developing cancer chemotherapeutic agents. Our group is looking at compounds of both natural and synthetic origin as potential source for developing topoisomerase I and II inhibitors. Historically, natural products have provided many successful new anti-cancer drugs (eg: doxorubicin, etoposide, taxol, gemcitabine). For the past quarter of a century, global marine sources have provided a vast array of new medicinally valuable natural products with anticancer activities. These natural products exist as secondary metabolites in marine invertebrates such as sponges, bryazoa, tunicates and ascidians. Several new experimental anticancer agents derived from marine natural products have entered advanced pre-clinical and clinical trials within the last decade. We are specifically working on developing new anti breast cancer agents derived from marine alkaloids that have shown inhibition of topoisomerase II.

Antibacterial Drug Discovery

S. aureus causes a variety of human infections, ranging from superficial abscesses to life threatening bacteremias.  Staphylococcal infections within the hospital and in the community are increasing, and an ever-growing number of antibiotic-resistant strains make treatment options difficult. Many of the nosocomial Methicillin-resistant S. aureus (MRSA) strains are multi-drug resistant, and even methicillin-sensitive strains can be deadly.  Notorious as a major source of nosocomial infections, S. aureus has recently taken on a new role in causing an escalating number of community-acquired infections in non-hospitalized persons without predisposing risk factors. New approaches for the prevention and treatment of bacterial infections require greater understanding of the molecular structures of the chosen intervention targets and of the pathogenic role played by the target in the infection process. Bacterial infections are very complex and involve the action of a large sophisticated arsenal of virulence factors, many of which are surface-bound. Surface proteins are one such virulence factor that plays a critical role in the infection process. The enzyme sortase catalyzes transpeptidation between sorting signals present in surface proteins destined to the bacterial surface and cross-bridge peptides in a cell wall precursor known as lipid II. Sortase-deficient strains, failing to anchor surface proteins, are found to be attenuated in their virulence. Hence, sortase is an attractive potential target for the discovery of new antibacterial agents. We hypothesize that Sortase inhibitors will render S. aureus nonadherent and consequently less virulent. By interrupting bacterial adherence, the initial step in the pathogenesis of bacterial infections, S. aureus will be poorly equipped to cause disease and may be more effectively cleared by host innate immune defenses and/or antibiotics.  

Teaching:

Dr. Velu's Course Pages are maintained at UAB Blackboard Vista. Lecture notes, recitations, assignments and links to OWL are available at this location.

Undergraduate Courses

• Organic Chemistry - I (CH-235)
• Organic Chemistry - II (CH-237)

Graduate Courses

• Special Topics: Chemistry of Natural Products (CH-772)
• Foundations of Organic and Inorganic Chemistry (CH-701)*
• Modern Drug Design and Development (IBS-708)*
• Organic Reactions and Synthesis (CH-732)*
• Medicinal Chemistry & Drug Discovery (CH-771)*

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* Team taught courses

UAB Affiliations and Co-appointments

• Associate Scientist, Comprehensive Cancer Center (CCC-UAB)
• Associate Scientist, Center for Clinical and Translational Science (CCTS-UAB)
• Member, Center for Biophysical Sciences and Engineering (CBSE-UAB)

Society Affiliations and Memberships

• American Association of Cancer Research (AACR)
• Society of Clinical and Translational Science (SCTS)
• American Chemical Society (ACS)
• American Heart Association (AHA)

Selected Publications:

1. Chenna, B.C.; King, J.R.; Shinkre, B.A.; Glover, A.L.; Lucius, A.L.; and Velu, S.E., Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors, European Journal of Medicinal Chemistry, 2010, INPRESS.
2. Ezell, S. J.; Li, H.; Xu, H.; Zhang, X.; Gurpinar, E.; Zhang, X.; Rayburn, E. R.; Sommers, C. I.; Yang, X; Velu, S. E.; Wang, W. and Zhang, R., Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent, Marine Drugs, 2010, IN PRESS.
3. Schormann, N.; Velu, S. E.; Murugesan, S.; Senkovich, O.; Walker, K.; Chenna, B.; Shinkre, B.; Desai, A. and Chattopadhyay, D.,  Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase, Bioorganic and Medicinal Chemistry, 2010, IN PRESS.
4. Wang, W.; Rayburn, E. R.; Velu, S. E.; Chen, D.; Nadkarni, D. H.; Murugesan, S.; Chen, D. and Zhang, R., A novel synthetic iminoquinone, BA-TPQ, as an anti-breast cancer agent: in vitro and in vivo activity and mechanisms of action, Breast Cancer Research and Treatment, 2010, IN PRESS.
5. Wang, F.; Ezell, S. J.; Zhang, Y.; Wang, W.; Rayburn, E. R.; Nadkarni, D. H.; Murugesan, S.; Velu, S. E. and Zhang, R., FBA-TPQ, a Novel Marine-Derived Compound as Experimental Therapy for Prostate Cancer, Investigational New Drugs, 2010, 28, 234-241.
6. Murugesan, S.;  Nadkarni, D. H.;  Velu, S. E., A facile synthesis of bispyrroloquinone and bispyrroloiminoquinone ring system of marine alkaloids, Tetrahedron Letters, 2009, 50, 3074-3076.
7. Wang, W.; Velu, S. E., Nadkarni, D. H.; Murugesan, S.; Rayburn, E. R. and Zhang, R.,  In Vitro and In vivo Anti-cancer Activity of Novel Synthetic Makaluvamine Analogues, Clinical Cancer Research, 2009, 15, 3511-3518.
8. Nadkarni, D. H.; Wang, F.; Wang, W.; Rayburn, E. R.; Ezell, S. J.; Murugesan, S.; Velu, S. E. and Zhang, R.,  Synthesis and In Vitro Anti-cancer Activity of Novel 1, 3, 4, 8-Tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one Alkaloid Analogues, Medicinal Chemistry, 2009, 5, 227-236.              
9. Kang, S.; Mou, L.; Velu, S. E.;  Brouillette, W. J.; Prevelige Jr., P. E., Synthesis of Biotin Tagged Chemical Cross-linkers and Their Applications for Mass Spectrometry, Rapid Communications in Mass Spectrometry, 2009, 23, 1719-1726.
10. Lee, Y. J.; King, J. R.; Chenna, B.; Owens Jr., S. B.; Freeman, J. L.; Gray, G. M. and Velu, S. E., Synthesis and the crystal structure of (E)-2-(7-(3-(thiophen-2-yl)acrylamido)-2,3-dihydro-5-oxobenzo[e][1,4]oxazepin-1(5H)-yl)ethyl acetate, Journal of Chemical Crystallography, 2009, 39, 902-907.
11. Patel, S. P.; Nadkarni, D. H.; Murugesan, S.; King, J. R. and Velu, S. E., Azide mediated detosylation of N-tosylpyrroloiminoquinones and N-tosylindole-4,7-quinones, Synlett, 2008, 2864-2868.
12. Schormann, N.; Senkovich, O.; Walker, K.; Wright, D. L.; Anderson, A. C.; Rosowsky, A.; Ananthan, S.; Shinkre, B. A.;  Velu, S. E. and  Chattopadhyay, D.,  Structure-based approach to pharmacophore identification, in silico screening and 3D-QSAR studies for inhibitors of Trypanosoma cruzi DHFR function, Proteins: Structure, Function, and Bioinformatics, 2008, 73, 889-901.
13. Chenna, B.; Shinkre, B. A.; Patel, S.; Owens Jr., S. B.; Gray. G. M. and Velu, S. E., Synthesis, separation and crystal structures of E and Z isomers of 3 - (2, 5- dimethoxyphenyl) - 2 - (4 - methoxyphenyl) acrylic acid.,  Journal of Chemical Crystallography, 2008, 38, 189-194.
14. Shinkre, B. A.; Raisch, K. P.; Fan, L.; Velu, S. E., Synthesis and Antiproliferative Activity of Benzyl and Phenethyl Analogs of Makaluvamines, Bioorganic and Medicinal Chemistry, 2008, 16, 2541-2549.
15. Chenna, B.,  Shinkre, B, A.,  King, J. R.,  Lucius, A. L.,  Narayana, S. V. L. and  Velu, S. E., Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A, Bioorganic and Medicinal Chemistry Letters, 2008, 18, 380-385.
16. Shinkre, B. A.; Nadkarni, D. H.; Owens Jr., S. B.; Gray, G. M. and Velu, S. E., Synthesis of E isomer and crystal structures of E & Z isomers of 3-(2, 5 - dimethoxyphenyl) - 2 - (4 - methoxyphenyl) acrylonitrile., Journal of Chemical Crystallography, 2008, 38, 205-209.
17. Shinkre, B. A.; Velu, S. E., Total synthesis of Secobatzelline B., Synthetic Communications,  2007, 37, (14), 2399-2409.
18. Velu, S. E.; Mou, L.; Luan, C. H.; Yang, Z. W.; DeLucas, L. J.; Brouillette, C. G.; Brouillette, W. J., Antibacterial nicotinamide adenine dinucleotide synthetase inhibitors: amide- and ether-linked tethered dimers with alpha-amino acid end groups. Journal of Medicinal Chemistry, 2007, 50, (11), 2612-21.
19. Shinkre, B. A.; Raisch, K. P.; Fan, L.; Velu, S. E., Analogs of the marine alkaloid makaluvamines: synthesis, topoisomerase II inhibition, and anticancer activity, Bioorganic and Medicinal Chemistry Letters, 2007, 17, (10), 2890-3.
20. Velu, S. E.; Luan, C. H.; Delucas, L. J.; Brouillette, C. G.; Brouillette, W. J., Tethered dimer inhibitors of NAD synthetase: parallel synthesis of an aryl-substituted SAR library. Journal of Combinatorial Chemistry, 2005, 7, (6), 898-904.
21. Velu, S. E.; Cristofoli, W. A.; Garcia, G. J.; Brouillette, C. G.; Pierson, M. C.; Luan, C. H.; DeLucas, L. J.; Brouillette, W. J., Tethered dimers as NAD synthetase inhibitors with antibacterial activity, Journal of Medicinal Chemistry, 2003, 46, (15), 3371-81.
22. Brouillette, W. J.; Bajpai, S. N.; Ali, S. M.; Velu, S. E.; Atigadda, V. R.; Lommer, B. S.; Finley, J. B.; Luo, M.; Air, G. M., Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: modifications of essential pyrrolidinone ring substituents, Bioorganic and Medicinal Chemistry 2003, 11, (13), 2739-49.
23. Dieter, R. K.; Lu, K.; Velu, S. E., Conjugate addition reactions of alpha-aminoalkylcuprates with a,b-alkenyl-, a,b-alkynyl-, a,b-b,g-allenyl-, and a,b-g,d-dienyl carboxylic acid derivatives, nitriles, and sulfoxides, Journal of Organic  Chemistry, 2000, 65, (25), 8715-24.
24. Dieter, R. K.; Velu, S. E., (a-Aminoalkyl)cuprates Prepared from Soluble Copper(I) Salts: Conjugate Additions to a,b-Unsaturated Carboxylic Acid Derivatives, Journal of Organic Chemistry  1997, 62, (12), 3798-3799.
25. Dieter, R. K.; Velu, S. E.; Nice, L. E., Regioselective control in the reactions of a-aminoalkylcuprates with allylic substrates. Synlett, 1997, (9), 1114-1116.
26. Dieter, R. K.; Nice, L. E.; Velu, S. E., Oxidation of a,b-enones and alkenes with oxone and sodium halides: a convenient laboratory preparation of chlorine and bromine. Tetrahedron Letters, 1996, 37, (14), 2377-80.
27. Jackson, Y. A.; Billimoria, A. D.; Velu, S., E.; Cava, M. P., Regioselective Amination of Indole-4,7-quinones, Journal of Organic Chemistry, 1995, 60, (11), 3543-5.
28. Velu, S., E.; Pillai, S. K.; Lakshmikantham, M. V.; Billimoria, A. D.; Culpepper, J. S.; Cava, M. P., Efficient Syntheses of the Marine Alkaloids Makaluvamine D and Discorhabdin C: The 4,6,7-Trimethoxyindole Approach, Journal of Organic Chemistry, 1995, 60, (6), 1800-5.
29. Parakka, J.P.; Velu, S., E. and Cava, M. P., A Novel o-Quinodimethane Tandem Diels - Alder Reaction.,        Journal of Organic Chemistry, 1994, 59, 4308 - 4310.