L. Koikov

The reaction of aryleneamines Ar(NMeâ)C=CHâ (Ar = Ph, 2-Py, 3-Py, 4-Py) with nitrosobenzenes p-RCâHâNO (R = H, Cl, Br, Me, MeO) in benzene or ether (20°C) is accompanied by rearrangement and leads to N¹, N¹-dimethyl-N²-aryl-2-oxo(aryl)-acetamidines (20-40%) and a mixture of products from reduction of the nitroso compounds. The effect of temperature on the yield of the amidines is insignificant, and

1. Some nicotinic antagonists (piperidine and quinuclidine derivatives and bis-quaternary compounds) protect early embryos of the sea urchin Lytechinus pictus against a calcium shock evoked by ionomycin or a mixture of phorbol myristate acetate and nicotine. 2. Maximal protective potency was found for drugs that did not penetrate the plasma membrane. 3. Early sea urchin embryos have nicotinic acetylcholine receptors (nAChR) or nAChR-like structures localized on the cell surface that, apparently, take part in the control of Ca2+ influx.

ABSTRACT Cultured human melanocytes respond to the melanocortin alpha-melanocyte stimulating hormone (alpha-MSH) with increased proliferation and melanogenesis, as well as survival after challenge with apoptosis inducers, such as ultraviolet radiation (UV) or hydrogen peroxide. We have compared the effects of two synthetic tetrapeptide analogs of alpha-MSH, Ac-His-D-Phe-Arg-Trp-NH2 and 4-phenylbutyryl-His-D-Phe-Arg-Trp-NH2 to those of alpha-MSH on cultured human melanocytes. We found that Ac-His-D-Phe-Arg-Trp-NH2 was a full agonist, with equal potency to alpha-MSH in stimulating tyrosinase activity. However, capping this tetrapeptide with 4-phenylbutyric acid resulted in a profound increase in its potency. Human melanocytes treated with this peptide at 0.01 nM exhibited a markedly higher tyrosinase activity than melanocytes treated with 1 nM alpha-MSH. Additionally, this peptide had a more prolonged effect than alpha-MSH, and was comparable with that of the best known alpha-MSH agonist NDP-alpha-MSH. 4-Phenylbutyryl-His-D-Phe-Arg-Trp-NH2 had a more remarkable anti-apoptotic effect than alpha-MSH on UV-irradiated human melanocytes, as determined by Annexin V staining and flow cytometric analysis. These effects of 4-phenylbutyryl-His-D-Phe-Arg-Trp-NH2 on melanocyte proliferation and tyrosinase activity are mediated by its binding to the MC1R, since they were totally abolished by concomitant treatment with a fragment analog of the physiological MC1R antagonist human agouti signaling protein. We propose that 4-phenylbutyryl-His-D-Phe-Arg-Trp-NH2 can be potentially used as a pigmentary agent that might protect human skin from the photodamaging effects of sun exposure.

It is shown by means of quantum-chemical calculations (MINDO/3) and data from the 13C NMR and photoelectron (PE) spectra that a weak interaction between the enamine fragment and the heteroring, which deviates from its plane, exists in pyridyl enamines. The reaction of (1-dimethylaminovinyl)pyridines with sulfene leads to mixtures of 3-dimethylamino-3-pyridylthietane 1,1-dioxide (80%) and the corresponding methylsulfonyl ketone, the yield of