A series of pyrido-1,2-thiazine derivatives of enamine type (E)-1 and the related triheterocycles 2, 3 were prepared and tested in vitro in a microbiological evaluation in our laboratories. It is worth noting that triheterocycles 2 and 3 belong to the new systems we described in 2004 [1] and here we present the first information about their pharmacological (microbiological) properties.

The (E)-configuration of enamines 1 and the structures of triheterocycles 2, 3 were assigned on the bases of IR, ¹H NMR, and X-ray data (in some cases) [1]. In this context it should be noted that triheterocycle 3 can be considered as an (Z)-analogue of (E)-enamines 1.

Eleven of new and described recently compounds 1 - 3 were tested against Mycobacterium fortuitum and Staphylococcus aureus. Activity against M. fortuitum correlates closely with that against M. tuberculosis and may be also used as a measure of anti-Mycobacterium tuberculosis activity because of the potential hazards of using M. tuberculosis [2].

Under microbiological evaluation, the compounds demonstrated no activity at the MIC₅₀ and MIC₉₀ levels, even at the maximal employed concentration (250 mg/mL), or their limited solubility prohibited an accurate determination.

However, to our complete surprise, most of the compounds tested helped to stimulate the growth of both M. fortuitum and S. aureus. The best stimulants enhanced the growth of the microorganisms within the range 10-50% at different concentrations of individual compounds (from 15.6 m g/mL to 250 mg/mL). It should be noted that for some of these compounds the effect of enhanced bacterial replication at a level of 10% was observed even at sub-m g/ml concentrations (0.03-0.45 mg/mL). However it is difficult to say if the stimulation observed at low concentration was a consequence of enhanced bacterial replication by the preparations or by a lack of activity of the compounds which allowed natural growth of the microorganisms.

On the basis of above data it may be concluded that the pyridothiazines of (E)-1 enamine type and derivatives of the new triheterocyclic systems 2 and 3 do not seem to be any specific antibacterial groups.

1. Malinka W., Karczmarzyk Z., Maczmarz M., Świątek P., Urbańczyk-Lipkowska Z.: Pol. J. Chem. 78 (815) 2004. 2) Remau T., Sanchez J., Shapiro M., Dever J., Gracheck S., Domagala J., J. Med. Chem., 1995, 38, 2974.

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