In order to impart antibacterial properties to microfibrous electrospun materials from styrene/maleic anhydride copolymers, quaternized chitosan derivatives (QCh) containing alkyl substituents of different chain lengths are covalently attached to the mats. A complete inhibition of the growth of bacteria, S. aureus (Gram-positive) and E. coli (Gram-negative), for a contact time of 30–120 min or a decrease of the bacterial titer by 2–3 log units is observed depending on the quaternization degree, the chain length of the alkyl substituent, and the molar mass of QCh. The modified mats are also effective in suppressing the adhesion of pathogenic S. aureus bacteria.
G-quadruplexes (GQs) have become valid targets for anticancer studies in recent decades due to their multifaceted biological function. Herewith, we aim to quantify interactions of potential heterocyclic ligands (Ls) with model GQs. For seven 4-aminoquinazolines and three 2-heteroaryl perimidines, seven of this ten-membered group so far unknown, we use routine quantum chemical modeling. As shown in the literature, a preferred mode of interaction of heterocycles with cellular structures is stacking to exposable faces of G-quadruplexes. To exploit the energy of this interaction as a molecular descriptor and achieve the necessary chemical precision, we use state of the art large-scale density functional theory (DFT) calculations of stacked heterocycles to a GQ. Actually, the GQ has been simplified for the computation by stripping it off all pentose phosphate residues into a naked model of stacked guanine quartets. The described model thus becomes computable. The obtained heterocyclic ligand GQ.L stacking energies, that is, their GQ affinities, are the necessary ligand descriptors. Using the ligand biological inhibitory activities (IC50) on a human malignant melanoma A375 cell line, we obtain a good linear relationship between computed ligand stacking affinities to GQ, and experimental log (IC50) values. Based on the latter relationship, we discuss a putative mechanism of anticancer activity of heterocyclic ligands via stacking interactions with GQs and thereby controlling cell regulatory activity. This mechanism may tentatively be applied to other condensed five- and six-membered small heterocycles as well.
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