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In the present study, 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 presence of formaline. To obtain the cyclic amine (morpholine, piperidine and pyrrolidine) derivatives of the 6th-position of chlorokojic acid derivatives, nucleophilic substitutions were carried out. Thereafter, 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. Efficacy of all these compounds has been compared to those of 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 (IC50: 11.26-68.58 µM) than the FDA-approved drugs except for vemurafenib. Fourteen of the compounds were proven to have higher IC50 values for the non-cancerous cell lines, HGF-1, and MRC-5 cells. Melanogenesis inhibition assay was performed to observe the ability of the drugs to inhibit melanin production and certain compounds were shown to be capable of actively inhibiting melanin production in melanoma cells. In conclusion, 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.

Purpose of review To discuss the crosstalk between the complement system and hemostatic factors (coagulation cascade, platelet, endothelium, and Von Willebrand Factor), and the consequences of this interaction under physiologic and pathologic conditions. Recent findings The complement and coagulation systems are comprised of serine proteases and are genetically related. In addition to the common ancestral genes, the complement system and hemostasis interact directly, through protein–protein interactions, and indirectly, on the surface of platelets and endothelial cells. The close interaction between the complement system and hemostatic factors is manifested both in physiologic and pathologic conditions, such as in the inflammatory response to thrombosis, thrombosis at the inflamed area, and thrombotic complications of complement disorders. Summary The interaction between the complement system and hemostasis is vital for homeostasis and the protective response of the host to tissue injury, but also results in the pathogenesis of several thrombotic and inflammatory disorders.

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Hepatocellular carcinoma is one of the most pervasive cancers with low prognosis, high frequency of recurrence, and metastasis. Studies conducted have focused on extricating novel strategies for successful treatment. Kojic acid and its derivatives are already proven to have depigmenting, anti‐inflammatory, and anti‐neoplastic properties. In the present study, kojic acid and its 10 distinct derivatives were tested on HEPG2 cell line for their possible anti‐cancer effect and seven of them were observed to be cytotoxic. Compound 6 was chosen to proceed as the IC50 dosage for HEPG2 cells was lower in comparison with the other derivatives and kojic acid itself. Further experiments pointed out that intrinsic apoptotic pathway was triggered with the exposure of the cells to IC50 concentration of the derivative as the treatment led to escalation of intracellular ROS, induction of TP53 gene, and activation of caspase 3/7. Pro‐apoptotic Jnk and Bax genes were not triggered suggesting that the apoptotic pathway advance through an alternative route. Complementary experiments are in need; howbeit, the current findings suggest that the derivative offers a novel promising approach against hepatocellular carcinoma as it is not detrimental to healthy cells within the concentrations applied, and it does not induce drug resistance.

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Oncul and Ercan: Difference of Breast Cancer Cells Regarding Apoptosis and MDRBreast cancer is one of the most common cancer types and malfunctioning proteins in apoptotic pathways are known to be the main contributors of cancer development. In this study MCF-7 and MDA-MB-231 breast cancer cell lines were treated with a potent chemotherapeutic agent, doxorubicin. IC 50 values were calculated to be 8306 and 6602 nM, respectively. Percentage of the cells in cell cycle arrest increased in a dose-dependent manner and was more evident in MDA-MB-231 cells. Apoptotic cell number increased in MCF-7 and Bax/Bcl-2 ratio was measured to be ~7 fold higher in cells treated with 200 nM of doxorubicin when compared to the control. Likewise, apoptotic cell rate increased in MDA-MB-231 cells and Bax/Bcl-2 ratio was increased by 2 fold compared to the control. Doxorubicin was also found to suppress Mdr-1 in a concentration-dependent manner and the outcome was more evident in MCF-7 cells. Drug efflux assay results were also shown to be consistent with Mdr-1 gene expression levels in both cell lines. Consequently it was concluded that doxorubicin directly influences apoptotic pathway and multidrug resistance in both MCF-7 and MDA-MB-231 cells even though data all together suggest that the effect is more significant on MDA-MB-231.