Novel Marine Compounds: Anticancer or Genotoxic?

In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers

IN SILICO MOLECULAR DOCKING ANALYSIS TO PREDICT THE ROLE OF METAL IONS IN THE FUNCTION OF DRUG TARGETED PROTEINS

Metal ions are required for many critical functions in living systems. Scarcity of some metal ions can lead to disease. A characteristic of metals is that they easily lose electrons from the familiar elemental or metallic state to form positively charged ions which tend to be soluble in biological fluids. Role of zinc, calcium and copper ions in the catalytic mechanism of drug targeted proteins such as Farnesyltransferase, Neuraminidase and Thioredoxin are analyzed using molecular docking, respectively. The docking results show that inhibitors have low Binding, docking and internal energies with proteins in the presence of Zn, Ca and Cu metal ions. However, in the absence of Zn, Ca and Cu metal ions these energies are increases. Metal plays a critical role in function of these proteins. Our results suggested that metal plays a particular role in the binding of the inhibitor with protein as well as structural stability and catalysis

Differential modulation of benzo[a]pyrene-derived DNA adducts in MCF-7 cells by marine compounds.

Despite several marine anticancer compounds to be DNA-interactive, causing from reductive DNA cleavage to DNA adduct formation, not much attention has been given to the DNA adduct as early biomarker in the screening and development of marine anticancer drugs. Most of these compounds have been tested in vitro by high-throughput cost-effective screening assays for their anticancer potential. In the present study, chemically diverse marine compounds were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells. Briefly, MCF-7 cells were incubated with the marine compounds, namely manzamine A, sarcophine, aaptamine, verongiaquinol, curcuphenol, and curcudiol (10, 50 and 100 μM) for 24 h followed by treatment with BP (0.5 μM). After 24 h re-incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by 32P-postlabeling technique. Interestingly, at 50 μM dose, only manzamine A, a probable antitumor compound, increased the BP-DNA adducts by 3-folds while curcuphenol and curcudiol lowered the BP-DNA adduction by up to 50%. Other compounds insignificantly modulated the BP-DNA adduction. At 10 μM, all the marine compounds were ineffective except aaptamine, which induced BP-DNA adduction by 2-fold. Further at 100 μM dose, all the compounds except manzamine A and verongiaquinol increased the BP-DNA adducts by up to 500%. In addition, verongiaquinol (50 μM) substantially down-regulated the levels of p53, p21, and p16, while manzamine A (50 μM), significantly inhibited the expression of p53. Aaptamine (50 μM) induced the p53 expression by 40%, however, other compounds were ineffective. All other marine compounds resulted in a differential response related to p21 and p16 expression