Kojik Asit Türevi Mannich Bazlarının Sentezi ve İnsan Melanoma Hücrelerine Etkisi ile Antitirozinaz Aktivitelerinin Araştırılması
Özet
Malign melanoma is malign tumour of melanin pigment, which gives colour of skin, eyes and hair. It has an increasing rate of incidence and high mortality. Tyrosinase is the enzyme responsible for melanin production in melanocytes and thereby pigmentation of skin and browning of fruits and vegetables. Abnormal production of melanin causes many problems, especially malign melanoma, hyperpigmentation, post-inflammatory pigmentation, melasma and skin aging. Inhibition of tyrosinase effects melanin production on a large scale. Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is a commonly used compound and well known with its antityrosinase property. However, there is need for better industrial applications and derivatives having optimal hydrophilic and lipophilic balance. For this purpose, within the scope of the thesis new fortyeight compounds having structure of 2-substituted-3-hydroxy-6-hydroxymethyl/chloromethyl/methyl/ morpholinomethyl/piperidinylmethyl/pyrrolidinylmethyl-4H-pyran-4-one were synthesized by modifying kojic acid, their structures were identified by using techniques IR, 1H-NMR, 13C-NMR, mass spectroscopy and elementary analysis. Also, some compounds having similar structure and published as a manuscript before, were included the study and totally sixty compounds examined for their mushroom tyrosinase inhibition and cytotoxic effects on A375 human melanoma cells, HGF-1 gingival cell line and MRC-5 cell line. Some of active compounds were also examined for indicating their effects on melanogenesis via intra-cellular melanin content in A375 cells by using a spectrophotometric method. Hereby, the relationship between antityrosinase activity, anticarcinogenic activity and melanogenesis inhibition was tried to clarified.
