mannich-bases and kojic-acid

Malignant melanoma is an agressive tumour related to the overproduction of melanin, which provides colors of skin, eyes and hair. In addition contributing to the risk of malignant melanoma, abnormal production of melanin has many drawbacks, including hyperpigmentation, post-inflammatory pigmentation, melasma and skin aging. Kojic acid is currently employed in order to lighten skin pigmentation and provide depigmentation.. Mannich bases of kojic acid with the structure of 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/ methyl/morpholinomethyl/piperidinylmethyl/pyrrolidinylmethyl-4H-pyran-4-one (compounds 1-23) were synthesized by the reaction of kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in the presence of formaline. To obtain the cyclic amine (morpholine, piperidine and pyrrolidine) derivatives, nucleophilic substitutions were carried out.. Cytotoxic effects on A375 human malignant melanoma, HGF-1 human gingival fibroblasts, and MRC-5 human lung cell lines were investigated by sulphorhodamine B assay. Control agents were vemurafenib, dacarbazine, temozolomide, and lenalidomide, which are the commercially available drugs for the treatment of malignant melanoma.. Cytotoxic action against melanoma cells was significantly more efficacious (IC. Mannich bases of kojic acid derivatives may be promising therapeutic agents, since some have more potent effects on melanoma cells than previously FDA-approved drugs for the treatment of malignant melanoma.

Topics: Antineoplastic Agents; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Mannich Bases; Melanins; Melanoma; Melanoma, Cutaneous Malignant; Pyrones; Skin Neoplasms; Spectrum Analysis

The Mannich base containing ciprofloxacin and kojic acid structural units was prepared and evaluated in antitumor activity. The enhancement in antitumor activity was observed both from the Mannich base (IC(50): 103.3±5.0 µM for HepG2, 87.9±8.0 µM for HCT-116 cell) and its copper complex (IC(50): 11.5±1.8 µM for HepG2, 44.4±2.5 µM for HCT-116 cell) compared to the ciprofloxacin and kojic acid. The mechanistic studies via RT-PCR, cell cycle analysis, mitochondrial membrane potential measurement, inhibition of topoisomerase and molecular docking indicated that there is a different molecular mechanism between the Mannich base and its copper complex. The cytotoxicity of the Mannich base was involved in apoptosis, cell cycle arrest, depolarization of mitochondrial membrane and weaker topoisomerase II inhibition, but the copper complex exerted its cytotoxicity mainly through dual topoisomerase inhibition, especially stabilizing the intermediate of cleavage DNA-topoisomerase complex.

Topics: Apoptosis; Cell Cycle; Cell Proliferation; Ciprofloxacin; Copper; Drug Screening Assays, Antitumor; HCT116 Cells; Humans; Mannich Bases; Neoplasms; Pyrones

Novel Mannich bases of 7-piperazinylquinolones with kojic acid and chlorokojic acid were designed as new quinolone antibacterials. All compounds showed significant in vitro antibacterial activity against both Gram-positive and Gram-negative bacteria. Particularly, chlorokojic derivative 2b was the most potent compound against Staphylococcus aureus and Pseudomonas aeruginosa (MIC values≤0.19 μg/mL). Its activity was 4-8 times more than that of standard drug norfloxacin. The molecular docking study of compound 2b further supported the molecular basis of the designed compounds.

Topics: Anti-Bacterial Agents; Mannich Bases; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Norfloxacin; Piperazines; Pyrones; Quinolones

A series of new 3-hydroxy-6-hydroxymethyl-2-substituted 4H-pyran-4-one derivatives were synthesized as potential anticonvulsant compounds. Mannich compounds were prepared by the reaction of appropriate substituted piperazine derivatives with kojic acid and formaline. The structure of the synthesized compounds was confirmed using the elementary analysis results and spectroscopic techniques such as IR, 1H-NMR and ESI-MS. Anticonvulsant activities of the synthesized compounds were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet) induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed according to procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies, 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-3-hydroxy-6-hydroxymethyl-4H-pyran-4-one (compound 11) against MES seizures and 3-hydroxy-6-hydroxymethyl-2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4H-pyran-4-one (compound 7) against scMet seizures were determined to be the most active compounds at all doses without neurotoxicity.

Topics: Animals; Anticonvulsants; Convulsants; Electroshock; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Mannich Bases; Mice; Neurotoxicity Syndromes; Pentylenetetrazole; Postural Balance; Pyrones; Seizures; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship

A series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antimicrobial and antiviral activities. Mannich base derivatives were prepared through the reaction of substituted piperazine or piperidine derivatives on chlorokojic acid and formaline. The structures of the synthesized compounds were confirmed by IR, (1)H and (13)C NMR, ESI-MS, and elemental analysis. According to the activity studies, compounds 2-7 (MIC: 1-2 microg/mL) were found to be highly active against Bacillus subtilis and Staphylococcus aureus, while compounds 3, 5 and 6 showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Also, compounds 2-7 were more remarkably active against Candida albicans and Candida parapsilosis (MIC: 4-8 microg/mL). Additionally, compound 2 was the most active one against RNA virus PI-3.

Topics: Animals; Anti-Infective Agents; Antiviral Agents; Bacteria; Cell Line; Chlorocebus aethiops; Drug Evaluation, Preclinical; Fungi; Herpesvirus 1, Human; Mannich Bases; Microbial Sensitivity Tests; Parainfluenza Virus 3, Human; Pyrones; Spectrum Analysis; Vero Cells