engleski

Spirobipyridopyrans, spirobinaphthopyrans, indolinospiropyridopyrans, indolinospironaphthopyrans and indolinospironaphtho-1,4-oxazines: synthesis, study of X-ray crystal structure, antitumoral and antiviral evaluation

The novel racemic indolinospirobenzopyrans (5- 7), indolinospironaphthopyrans (11-14) and indolinospironaphtho-1, 4-oxazine (17) were synthesized by an aldol type of condensation of 1', 3', 3'-trimethyl-2'-methyleneindoline and its 5-substituted derivatives with an appropriately substituted hydroxybenzaldehyde, hydroxynaphthaldehyde or nitrosonaphthol. An unequivocal proof of the stereostructures of 9 and 17 was obtained by the single-crystal X-ray diffraction method. A substituted indoline ring and the benzopyran ring in 9 and the naphtho-1, 4-oxazine moiety in 17 are interconnected via the common chiral atom and positioned almost perpendicularly to each other. The five- membered 2, 3-dihydropyrrolo moiety of the indoline ring adopts an envelope conformation in both structures. Of all the compounds of this series, indolinospirobenzopyran (9), containing a methoxy group at the position 6 of the benzopyran ring, exhibited the most pronounced inhibitory effects on the growth of human CEM (IC50: 0.68 mg/ml) and Molt4/C8 (IC50: 0.71 mg/ml) cells. Spirobipyridopyran (1) inhibited specifically the growth of human melanoma (HBL) (IC50: 0.9 mM) cells but not the growth of normal fibroblasts (WI38). The best cytostatic activity was achieved with the compounds 8, 9 and 10, from the class of indolinospirobenzopyrans. The indolinospirobenzopyrans 4, 6-8, 10 and the indolinospironaphtho-1, 4-oxazine 16 showed, albeit modest, selectivity as antiviral agents against varicella-zoster virus (VZV) and/or cytomegalovirus (CMV) (EC50 within the concentration range of 0.4-4 µ ; ; ; g/ml).

spiropyrans ; 1H and 13C NMR spectra ; single crystal X-ray analysis ; cytostatic activities ; antiviral activities

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