Chemicals and Drugs Commons^™

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Asymmetric Total Synthesis Of Congeners Of Hydramycin, An Anthraquinone-Type Antitumor Agent, Costyl Ngnouomeuchi Njiojob

Doctoral Dissertations

Hydramycin is an antitumor antibiotic isolated from Streptomyces violaceus. It is a pyranoanthraquinone-type antitumor agent that has shown broad-spectrum activity against a variety of human-derived cancer cell lines. Among tumors evaluated at the National Cancer Institute (lung, colon, melanoma, breast and prostate), GI₅₀s were <10⁻¹⁰ M in the NCI's 60-cell-line panel. We embarked on the synthesis and evaluation of a simplified congener 2-(1-hydroxy-1-(oxiran-2-yl)ethyl)-4H-naphtho[2,3-h]chromene-4,7,12-trione(17), which would facilitate synthesis while retaining the potent activity. Hydramycin has two chiral centers, and our goal is to design and synthesize all the possible enantiomers (four in …