Ascidians (tunicates) contain compounds with a large range of pharmacological activities. With the most? common of chemical ingredients, elemental sulfur and dopamine, an ascidian has developed a means to? protect itself from predators using in essence chemical warfare. With lessons that marine organisms can? provide, how might chemists seek the advent of new therapeutic substances from abundant and simple? natural reagents? The problem is that we lack an understanding of the biosynthetic pathways that marine? organisms use to make protective or otherwise purposeful molecules from benign common precursors. A? long-term objective of this program is to synthesize sulfur?dopamine compounds that may have enhanced? biological activity compared to what nature provides. This proposal outlines an experimental and theoretical? organic chemistry approach to addressing the structure and synthesis of polysulfane antitumor compounds.? Mechanistic information will be sought in reactions that mimic a biosynthetic process to help in designing? new drugs. The goals of the research project are: (1) to examine the chemical mechanism for the formation? of natural product antitumor polysulfanes formed from dopamine, and determine the product yields and? product reaction profiles, (2) to identify the chemical form of sulfur that can add to dopamine and related? natural aromatics such as catechol, (3) to define certain steps in the mechanism of formation of the? polysulfur linkage, (4) to determine whether observed trends in heterocycle odd-even membered ring effects? serve as a guide in the synthesis of pharmaceutically active polysulfane molecules, (5) to synthesize? sulfur?dopamine compounds that have enhanced biological activity compared to what nature provides, and? (6) to establish a collaborative research program such that the molecules produced in our laboratory will be? examined as possible lead compounds, which may eventually be used clinically as antitumor and antibiotic? agents. Research design and methods will involve experiments that utilize HPLC, GC/MS, NMR, and kinetic? analyses for characterizations of the mechanisms. Theoretical calculations will be performed to discover the? factors that are likely to influence polysulfane synthesis and decomposition with the aim of evaluating the? viability of the intermediates.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Minority Biomedical Research Support - MBRS (S06)
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Minority Programs Review Committee (MPRC)
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Brooklyn College
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Jarzecki, Andrzej A (2012) Quantum-mechanical study of lead coordination in sulfur-rich proteins: mode and structure recognition in UV resonance Raman spectra. J Phys Chem A 116:571-81
Martinez, Alberto; Suarez, Javier; Shand, Tiffany et al. (2011) Interactions of arene-Ru(II)-chloroquine complexes of known antimalarial and antitumor activity with human serum albumin (HSA) and transferrin. J Inorg Biochem 105:39-45
Mahendran, Adaickapillai; Kopkalli, Yasemin; Ghosh, Goutam et al. (2011) A hand-held fiber-optic implement for the site-specific delivery of photosensitizer and singlet oxygen. Photochem Photobiol 87:1330-7
Navarro, Maribel; Castro, William; Martinez, Alberto et al. (2011) The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects and increased drug lipophilicity enhance heme aggregation inhibition at lipid/water interfaces. J Inorg Biochem 105:276-82
Liu, Fangwei; Anis, Reema; Hwang, Eunmi et al. (2011) Group 11 Metal Compounds with Tripodal Bis(imidazole) Thioether Ligands. Applications as Catalysts in the Oxidation of Alkenes and as Antimicrobial Agents. Molecules 16:6701-20
Gonzalez, Marlyn; Goddard, Noel; Hicks, Charles et al. (2010) A screen for deficiencies in GPI-anchorage of wall glycoproteins in yeast. Yeast 27:583-96
Aebisher, David; Zamadar, Matibur; Mahendran, Adaickapillai et al. (2010) Fiber-optic singlet oxygen [1O2 (1Delta(g))] generator device serving as a point selective sterilizer. Photochem Photobiol 86:890-4
Martinez, Alberto; Rajapakse, Chandima S K; Sanchez-Delgado, Roberto A et al. (2010) Arene-Ru(II)-chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells. J Inorg Biochem 104:967-77
Zamadar, Matibur; Aebisher, David; Greer, Alexander (2009) Singlet oxygen delivery through the porous cap of a hollow-core fiber optic device. J Phys Chem B 113:15803-6
Jarzecki, Andrzej A (2009) Quantum-mechanical calculations of resonance Raman intensities: the weighted-gradient approximation. J Phys Chem A 113:2926-34

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