Regioselectivity and tautomerism of novel five-membered ring nitrogen heterocycles formed via cyclocondensation of acylthiosemicarbazides.

A series of 1-acyl-4-phenyl/(acridin-9-yl)thiosemicarbazides 3, including four new compounds, were prepared in order to study substituent effects on cyclization reactions with oxalyl chloride (producing imidazolidine-4,5-diones 4), dimethyl acetylenedicarboxylate (to give thiazolidin-4-ones 7 and 8) and autocondensation under alkaline conditions (to yield 1,2,4-triazoles 9). A positional isomer, 10 of compound 3f was also prepared. Altogether, twenty new compounds characterized and identified by IR, UV,1H, 13C and 2D NMR and quantum chemical calculations are described. The tautomerism of the products and regioselectivity of the reactions were evaluated. Compounds 3f-h,3h.2HCl, 7b,d and 10 were screened for cytotoxic activity against the L1210 leukemia cell line and all compounds, except for 3f, exhibited promising inhibitions of cell growth.

Acridine derivatives inhibit lysozyme aggregation.

We have screened a library of structurally distinct acridine derivatives (19 compounds) for their ability to inhibit lysozyme amyloid aggregation in vitro. Studied acridines were divided into three structurally different groups depending on the molecule planarity and type of the side chain-planar acridines, spiroacridines and tetrahydroacridines. Thioflavine T fluorescence assay and transmission electron microscopy were used for monitoring the inhibiting activity of acridines. We have found that both the structure of the acridine side chains and molecule planarity influence their antiamyloidogenic activity. The planar acridines inhibited lysozyme aggregation effectively. Spiroacridines and tetrahydroacridines had no significant effect on the prevention of lysozyme fibrillization, probably resulting from the presence of the heterocyclic 5-membered ring and non-planarity of molecule. Moreover, in the presence of some tetrahydroacridines the enhanced extent of aggregation was detected. We identified the most active acridine derivates from studied compound library characterized by low micromolar IC50 values, which indicate their possible application for therapeutic purpose.