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Heterocyclic compounds with chromane- and indole-type skeleton represent two fairly large groups of substances with proved beneficial antioxidant effects even beyond the nutritional base. Although these compounds have usual origin in the nature, a rational chemical synthesis might offer an efficient tool for “playing” with their physico-chemical properties so as to optimize their biological effects. In the present study, on using the cellular models, we tried to evaluate the potential of chemically modified flavonoids and synthetic hexahydropyridoindoles to ameliorate ageing-related degenerative processes. Introduction of electron-accepting quinonoid substituent into quercetin increased its prooxidant capacity and toxicity, however, at lower concentration, the effects encompassing hormesis were observed. These properties involved enhanced protection of human fibroblast-like cells from oxidative insult as well as anti-inflammatory effects. 3´-O-Acylation of quercetin (ensuring its higher lipophilicity) yielded in enhanced protection of adult rat microglial cells based on suppression of their protein oxidation, downregulation of the cellular senescence markers and induction of a resting, ramified morphology. On the other hand, weakly basic piperidine moiety in pyridoindoles appeared to steer these substances into lysosomal compartments via a proton-trap mechanism, this being followed by their enhanced accumulation. This mechanism yielded in increased staining of the cells, induction of osmotic processes and enhanced protection of the macrophageous cells from oxidative damage. Thus, rational synthetic variations of indole- and chromane-type compounds can facilitate the search for the substances showing enhanced interference in ageing-related pathologies. This is to say, there are numerous modifications susceptible to optimize either specific targeting, bioavailability or electron properties of these hopeful biological molecules [VEGA2/0031/12].