mannich-bases and Melanoma

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