Ade Arsianti

Synthesis and biological activity of 2-hydroxynicotinoyl-serine-butyl esters related to antibiotic UK-3A

Novel 2-hydroxynicotinoyl-serine-butyl esters have been synthesized. Three-step reactions from L-serine by esterification with n-butanol, amidation with 2-hydroxynicotinic acid and esterification with the corresponding carboxylic acids gave AD-1, AD-2 and AD-3. The toxicity level of esters were determined by Brine shrimp assay, and antibiotic activity was tested against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Candida albicans. AD-3 showed greater activity as a growth inhibitor of B. subtilis and S. aureus compared to Antimycin A(3).

Anti-hepatitis C virus activity of a crude extract from longan ( Dimocarpus longan Lour.) leaves

Infection with hepatitis C virus (HCV) results in hepatitis C, a disease characterized by chronic infection, cirrhosis, and hepatocellular carcinoma. Currently, the standard therapy is a combination of pegylated interferon-α plus ribavirin with NS3 protease inhibitors. Addition of NS3 protease inhibitors to the standard therapy improves response rates; however, use of NS3 protease inhibitors is also associated with significant adverse effects and an increase in the overall cost of treatment. Therefore, there is a need to develop safe and inexpensive drugs for the treatment of HCV infections. In this study, we examined the antiviral activity of a crude extract from Dimocarpus longan leaves against HCV (genotype 2a strain JFH1). The D. longan crude extract (DL-CE) exhibited anti-HCV activity with a 50% effective concentration (EC50) of 19.4 μg/ml without cytotoxicity. A time-of-addition study demonstrated that DL-CE has anti-HCV activity at both the entry and post-entry steps and markedly blocks the viral entry step through direct virucidal activity with marginal inhibition of virion assembly. Co-treatment of DL-CE with cyclosporine A, an immunosuppressant or telaprevir, an NS3 protease inhibitor, resulted in additive and synergistic antiviral effects, respectively. Our findings suggest that DL-CE may be useful as an add-on therapy candidate for treating HCV infections.

In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. How-ever, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect an-timycin A3 and its analogue to induce apoptosis in those cells. Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer. Results and Conclusion: Open-chain analogues of antimycin A3 were successfully syn-thesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharp-less asymmetric dihydroxylation. Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of an-timycin A3 as a promising candidates of new anti-laryngeal cancer agents.