Molecular modification approach on kojic acid derivatives as antioxidants related to ascorbic acid.

A hypothetical study by using molecular modeling for antioxidant capacity of kojic acid derivatives was performed using quantum chemistry calculations by DFT/B3LYP/6-311++G(3d,2p). Four modification approaches were considered namely simplification, functional modifications, ring regioisomerism, and hydroxylation. Molecular orbitals, single-electron transfers, hydrogen atom transfers, and spin density distributions were used for antioxidant prediction. In accordance with HOMO, LUMO, Gap, ionization potential, bond dissociation energy, and stabilization energy, the molecular simplifications of kojic acid show that enol moiety is more important for antioxidant capacity than alcohol group. Few molecular modifications on alcohol or enol position were more potent than kojic acid. The π conjugation system among ether, alkene, and hydroxyl moieties can be involved on resonance effects of better compounds. A different performance was observed on alcohol molecular modifications when compared to enol position. All lactone derivatives were more potent than kojic acid on both mechanisms, and their hydroxylated derivatives were more potent than ascorbic acid. In conclusion, the ring regioisomers and its hydroxylated derivatives have better antioxidant capacity than kojic acid. Graphical Abstract The theoretical study using molecular modeling for antioxidant capacity prediction of kojic acid was more related to enol moiety than alcohol. The regioisomerism and hybrid derivatives show that the lactone derivatives increase antioxidant capacity more than the pyrone derivatives.

Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.

A drug design for safer phenylbutazone was been explored by reactivity and docking studies involving single electron transfer mechanism, as well as toxicological predictions. Several approaches about its structural properties were performed through quantum chemistry calculations at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and ionization potential were associated to electron donation capacity. The spin densities contribution showed a preferential hydroxylation at the para-positions of phenyl ring when compared to other positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than alkyl hydroxylation. Docking studies indicate that six structures 1, 7, 8 and 13⁻15 have potential for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed are potentially more active as well safer than phenylbutazone and only structures 8 and 13⁻15 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.