Medicinal Chemistry

Prostate cancer is one of the most common cancer types among males. Metastasis in advanced stages of prostate cancer makes the disease refractory to current treatments and is the leading cause of death of advanced prostate cancer. Drugs targeting metastasis may provide new therapeutic strategies for advanced prostate cancer. We identified the traditional antihelminthic drug niclosamide to have great potential in suppressing the metastatic process of prostate cancer. The drug potently inhibited the migration and invasion of the DU145 prostate cancer cell line. It significantly suppressed the protein levels of key members of the matrix metalloproteinase family (MMP2 and MMP9), as well as cadherins and catenins (E-/N-cadherin and β-catenin), all of which are critical factors in the metastastic process. Further investigation suggested that the motility inhibition of niclosamide on DU145 cells was highly correlated to its suppression of the STAT3 and MAPK signaling pathways.

There are several in vitro methods for evaluating antioxidant activity. This review article gives information regarding different methods that are used to measure the antioxidant defense system In addition; the advantages and shortcomings, as well as the specific cases of their application also are demonstrated. The chemical principles of methods based on biological oxidants comprise superoxide radicals scavenging (O2 ·-); hydroxyl radical scavenging (HO.); hydrogen peroxide scavenging (H2O2); peroxyl radical scavenging (ROO.) and nitric oxide scavenging (NO.). Among the non-biological testing can highlight scavenging of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH• assay) and scavenging of 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical cation (ABTS assay). Furthermore, thiobarbituric acid reactive substances (TBARS) and protein carbonyl assays also have been described. This article will be a comprehensive ready reference for those who are interested on antioxidant study.

Quercetin, a kind of flavonoids, exerts the cardiovascular actions. In guinea pig ventricular cardiomyocytes, quercetin depresses the action potential duration (APD) and inhibited the underlying ionic currents ICaL.,IKrec. IK1 in cardiomyocytes. In rat aorta, quercetin (0.1 to 100 μM) relaxed the contraction induced by pretreatment with 5 μM norepinephrine (NE) in aconcentration-dependent manner. NG-monomethyl-L-arginine acetate (L-NMMA) at 100 μM reduced the quercetin (100 μM)-induced vasorelaxation from 97.0 ± 3.7% (n=10, p<0.05) to 78.0 ± 11.6% (n=5, p<0.05). Endothelium removal as well attenuated the vasodilatation. In the presence of both 100 μM L-NMMA and 10 μM indomethacin, the quercetin-induced vasorelaxation was further attenuated by high K (30 mM) or 10 μM tetraethylammonium (TEA). Among KCa channel inhibitors, the quercetin-induced vasodilatation was attenuated by 0.3 μM apamin (sensitive to SK), but not by 30 nM charybdotoxin (sensitive to BK and IK). Under KCl-induced vasoconstriction, the quercetin-induced vasorelaxation was attenuated by PK-C inhibitors; Gö6983 (α-, β-, γ-, δ and ζ-sensitive) produced stronger than Ro-31-8425 (α-, β-, γ- and ε-sensitive). In rat mesenteric artery, the quercetininduced vasodilatation was almost resistant to both 100 μM L-NG-nitro arginine methyl ester (L-NAME) and 100 μM indomethacin. The L-NAME/indomethacin-resistant quercetin-induced   was not modified by TEA (1 mM), but was attenuated by endothelium removal and 100 μM 18α- and 50 μM 18β-glychrrhetinic acids (gap junction inhibitors). Therefore, quercetin dilates the vascular smooth muscle mediated by endothelium-dependent and -independent mechanisms.

We describe the case of a 69-year-old female who developed pancytopenia and acute hepatitis as a complication of intravesical BCG instillations for the treatment of bladder urothelial carcinoma. Liver and bone marrow biopsies revealed multinucleated giant epithelioid cells and non-caseating granulomas. Treatment with antituberculosis drugs achieved complete resolution. This case illustrates an infrequent but severe complication of intravesical BCG instillations, whichcan be successfully treated without steroids.

Myrianthus arboreus P. Beauv. (Cecropiaceae) and Alchornea cordifolia (Schum. & Thonn.) Muel. Arg. (Euphorbiaceae) are tropical plants used for the treatment of ailments such as diarrhoea, malaria, boils, dysentery, wounds and skin infections. The study investigated the antimicrobial, antioxidant and wound healing properties of methanol leaf extract of M. arboreus (MLMA), aqueous (AqLAC) and ethanol leaf extracts (ELAC) of A. cordifolia. The antimicrobial activity of the extracts was examined using the agar diffusion and micro-dilution methods against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 4853, Staphylococcus aureus ATCC 25923, Bacillus subtilis NTCC 10073 and clinical strain of Candida albicans. Antioxidant property of the extracts was determined by DPPH method and wound healing property of the extracts determined using excision wound model. MLMA exhibited activity against S. aureus, B.subtilis, E. coli, P. aeruginosa and C. albicans with MIC values of 8.0, 6.0, 8.0, 10.0 and 6.0 mg/mL, respectively. ELAC showed good antimicrobial activity against S. aureus, B.subtilis, E. coli, P. aeruginosa and C. albicans with MICs of 3.0, 4.0, 6.0, 4.0 and 4.0 mg/mL respectively; and AqACL had MICs of 2.5, 3.0, 10.0, 4.0 and 3.0 mg/mL, respectively. The IC50 of MLMA, AqACL and ELAC were 2.68, 0.79, 0.78 μg/mL respectively. The extracts (5% w/w AqACL and 10% w/w MMAL extract creams) showed potent wound healing capacity with better wound closure (p<0.05) at day 1 and day 9 (p<0.001) compared with untreated wounds. Histological investigations showed enhanced wound tissue proliferation, fibrosis and re-epithelization compared with the untreated wound tissues. Phytochemical screening of extracts revealed the presence of tannins, alkaloids, glycosides, terpenoids and flavonoids. The biological activities of the extracts from the two plants may justify their uses in treatment for microbial infections and wounds.