Organotin compounds (OTs) are widely used in many societal processes and have recently been identified in the blood of > 80% of the US population where they can have a profound negative impact upon human natural killer cell (NKC) function. We will address this critical health-related problem. Using SCORE support we have shown that the simple structural motif of an S or O atom within the molecular structure of certain OTs (permitting an intramolecular self-association between the Sn and S(O)) dramatically reduces the impact of the OT upon the NKCs and augments biological targetting. We propose to synthesize OTs containing 2 and 3 S(O)(N)-containing aryl and alkyl ligands to augment this protection including 14C/fluorophore tagged species for biochemical tracking. This program of synthesis will be augmented by an antibacterial assessment that has proven very indicative of OT structure-reactivity relationships. A collaborative evaluation of the OT impact upon NKCs with Professor Margaret Whalen (Tennessee State University) will be continued. In tandem with this program of synthesis and biological evaluation we shall test the new materials to assess their capacity to provide the societal uses that make tin the element with the largest number of individual derivatives used in modern society. Thus, e.g., polymer formation, curing and stabilization will be evaluated using the appropriate and recognized techniques to show that the weak intramolecular Sn.S(O)(N) interactions, while enough to have a profound solid-state structural and biological impact will not remove their industrial roles. In collaboration with Dr. Renato Aguilera (U. T. El Paso) we have preliminary results that demonstrate the presence of the intramolecular Sn..S motif does not remove the capacity of selected OTs to inhibit the growth of uterine cancer HeLa (GFP) cells. Since there is much interest in OTs as anti-tumor agents this result is most promising, i.e. excellent anti-tumor activity with significantly reduced anti-HKC activity. Also, a recent report on the efficacy of OTs as anti-parasitics against Leishmania donovani, will be evaluated in collaboration with Dr. Rosa Maldonado (U. T. El Paso) since in our region, SW-USA with large immigration from Central/South America where such parasites are endemic, this is a problem of growing concern. Letters agreeing to the collaborations are attached.
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