Organotin compounds (OTs) are widely used in many societal processes and have recently been identifiedin the blood of > 80% of the US population where they can have a profound negative impact upon humannatural killer cell (NKC) function. We will address this critical health-related problem. Using SCORE supportwe have shown that the simple structural motif of an S or O atom within the molecular structure of certainOTs (permitting an intramolecular self-association between the Sn and S(O)) dramatically reduces theimpact of the OT upon the NKCs and augments biological targetting. We propose to synthesize OTscontaining 2 and 3 S(O)(N)-containing aryl and alkyl ligands to augment this protection including14C/fluorophore tagged species for biochemical tracking. This program of synthesis will be augmented by anantibacterial assessment that has proven very indicative of OT structure-reactivity relationships. Acollaborative evaluation of the OT impact upon NKCs with Professor Margaret Whalen (Tennessee StateUniversity) will be continued. In tandem with this program of synthesis and biological evaluation we shall testthe new materials to assess their capacity to provide the societal uses that make tin the element with thelargest number of individual derivatives used in modern society. Thus, e.g., polymer formation, curing andstabilization will be evaluated using the appropriate and recognized techniques to show that the weakintramolecular Sn.S(O)(N) interactions, while enough to have a profound solid-state structural and biologicalimpact will not remove their industrial roles.In collaboration with Dr. Renato Aguilera (U. T. El Paso) we have preliminary results that demonstrate thepresence of the intramolecular Sn..S motif does not remove the capacity of selected OTs to inhibit thegrowth of uterine cancer HeLa (GFP) cells. Since there is much interest in OTs as anti-tumor agents thisresult is most promising, i.e. excellent anti-tumor activity with significantly reduced anti-HKC activity. Also, arecent report on the efficacy of OTs as anti-parasitics against Leishmania donovani, will be evaluated incollaboration with Dr. Rosa Maldonado (U. T. El Paso) since in our region, SW-USA with large immigrationfrom Central/South America where such parasites are endemic, this is a problem of growing concern. Lettersagreeing to the collaborations are attached.
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