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• New Mannich bases of kojic acid were synthesized. • Ten compounds have shown higher antityrosinase activities than the reference compound. • Inhibition is provided by the complex formation between hydroxymethyl group and copper ions. • The inhibition mechanism is based on the metal complex, H-bond and hydrophobic interactions. • The present results support hypothesis that compounds can be promising antityrosinase agents. Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4 H -pyran-4-one structure (compounds 1 – 30) with inhibitory effects on tyrosinase enzyme were described. One-pot Mannich reaction was carried out by using kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in presence of formaline. Subsequently, cyclic amine (morpholine, piperidine and pyrrolidine) derivatives of the 6th-position of chlorokojic acid were obtained with nucleophilic substitutions in basic medium. The structures of new compounds were identified by FT-IR, 1H- and 13C NMR, ESI-MS and elemental analysis data. The potential mushroom tyrosinase inhibitory activity of the compounds were evaluated by the spectrophotometric method using l -DOPA as a substrate and kojic acid as the control agent. The potential inhibitory activity was also investigated in silico using molecular docking simulation method. Tyrosinase inhibitory action was significantly more efficacious for several compounds (IC 50 : 86.2–362.1 µM) than kojic acid (IC 50 : 418.2). Compound 3 bearing 3,4-dichlorobenzyl piperazine moiety was proven to have the highest inhibitory activity. The results of docking studies showed that according to the predicted conformation of compound 3 in the enzyme binding site, hydroxymethyl group provides a metal complex with copper ions and enzyme. Thus, this interaction explain the high inhibitory activities of the compounds 1 , 3 and 4 possessing hydroxymethyl substituent supporting the mushroom assay results with docking studies. In accordance with the results, it is suggested that Mannich bases of kojic acid bearing substituted benzyl piperazine groups (compounds 1 , 3 , 4 , 11 , 13 , 14 , 23 , 24 , 28 , and 29) could be promising antityrosinase agents. Additionally, considering the relationship between tyrosinase inhibitory activity results and molecular docking, a new tyrosinase inhibition mechanism can be proposed. [ABSTRACT FROM AUTHOR]

• New fluoroquinolones were designed as anti-tuberculosis and antibacterial agents. • 21 new moxifloxacin derivatives were synthesized and characterized. • MICs were determined vs. M. tuberculosis H37Rv and several bacteria and fungi. • Selected compounds were further investigated as DNA gyrase inhibitors. • Docking studies were performed to understand the binding modes of the leads. Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, 1H NMR, 13C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00–0.39 µg/mL while compounds 1 , 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1 – 21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC 50 value of <1.23 μg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus. [ABSTRACT FROM AUTHOR]