Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives.

BACKGROUND: Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications. OBJECTIVE: To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity. METHOD: The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay. RESULTS: A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 µM) than that of 5-Fluorouracil (10-17 µM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein. CONCLUSIONS: We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling.

New Pyrano[2,3-d:6,5-d']dipyrimidine Derivatives-Synthesis, in vitro Cytotoxicity and Computational Studies.

A new series of pyrano[2,3-d:6,5-d']dipyrimidine derivatives were synthesized and evaluated for their in vitro anticancer activity. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, 15N NMR, HR-MS and FT-IR spectral analyses. The cytotoxic activities of these compounds against four human cancer (HeLa, SKBR-3, HepG2, and Caco-2) cell lines were determined. The synthesized compounds showed high selectivity, and four compounds (5e, 5f, 5g and 5i) showed excellent potent cytotoxicity against HeLa, SKBR-3, and HepG2 cancer cell lines. Furthermore, four other compounds (5a, 5c, 5b and 5d) have exhibited significant cytotoxicity activity in the SKBR-3 and HepG2 cell lines respectively, with moderate cytotoxicity seen in the HeLa cell line. Additionally, a molecular docking study was conducted to predict the anti-cancer behavior of the synthesized compounds via inhibition of the allosteric site of Human Kinesin Eg5.

PEGylated galactosylated cationic liposomes for hepatocytic gene delivery.

The efficiency of liposome-mediated gene delivery is greatly enhanced by appropriate decoration of vehicles with cell-specific targeting ligands. However, liposome-DNA complexes may still be opsonized in serum thus ablating any advantage gained. A stealth aspect may therefore be conferred on complexes by poly(ethylene glycol) (PEG) grafting. Here, we examined the effect that degree of PEGylation has on physicochemical properties, cytotoxicity and transfection activity of lipoplexes containing the cytofectin 3ß-[N-(N', N'-dimethylaminopropane)-carbamoyl] cholesterol (Chol-T), the neutral co-lipid dioleoylphosphatidylethanolamine (DOPE), the asialoglycoprotein receptor (ASGP-R) targeted cholesteryl-ß-d-galactopyranoside (Chol-ß-Gal) ligand, and plasmid DNA in ASGP-R-negative (HEK293) and receptor-positive (HepG2) human cell lines. Lipoplexes were characterized by hydrodynamic sizing, electron microscopy, band shift, ethidium bromide (EtBr) intercalation and nuclease digestion assays. Cryo-TEM and DLS studies revealed that PEGylation generated smaller and more densely aggregated lipoplexes than their non-PEGylated counterparts. MTT and AB reduction studies showed that the lipoplexes elicited a dose-dependent cytotoxic effect in both cell lines, with cell viability remaining above 65% (MTT) and 50% (AB). The Ricinus communis (RCA120) agglutination test confirmed that the galactosyl residues on the targeted lipoplexes were well exposed and accessible. Transgene activity increased by 63% and 77% when HepG2 was confronted by the 2 and 5mole% PEGylated lipoplexes, respectively, compared to their non-PEGylated counterparts. Furthermore, Chol-T Chol-ß-Gal 5% PEG complexes were able to achieve a 164% increase in transfection level in the ASGP-R positive cell line (HepG2) compared to HEK293 (ASGP-R negative). Results strongly indicate that PEGylation potentiates the activity of ASGP-R-targeted lipoplexes, highlighting their gene delivery potential.

Assessment of physico-chemical qualities and heavy metal concentrations of Umgeni and Umdloti Rivers in Durban, South Africa.

We assessed the effects of seasonal dynamics on the physico-chemical qualities and heavy metals concentrations of the Umgeni and Umdloti Rivers in Durban, South Africa. Water samples were taken from nine different sampling points and analysed for the following parameters; temperature, pH, turbidity, electrical conductivity (EC), biological oxygen demand (BOD5), chemical oxygen demand (COD), phosphate (PO4(2-)), nitrate (NO3(2-)), ammonium (NH4(+)), sulphate (SO4(2-)), lead (Pb(2+)), mercury (Hg(2+)), cadmium (Cd(2+)), aluminium (Al(3+)), and copper (Cu(2+)) using standard methods. The data showed variations it terms of the seasonal fluctuations and sampling regime as follows: temperature 12-26.5 °C; pH 5.96-8.45; turbidity 0.53-18.8 NTU; EC 15.8-5180 mS m(-1); BOD5 0.60-7.32 mg L(-1); COD 10.5-72.9 mg L(-1); PO4 (2-) < 500-2,460 µg L(-1); NO3 (2-) <0.05-4.21 mg L(-1); NH4 (+) < 0.5-1.22 mg L(-1); SO4 (2-) 3.90-2,762 mg L(-1); Pb(2+) 0.023-0.135 mg L(-1); Hg(2+) 0.0122-0.1231 mg L(-1) Cd(2+) 0.068-0.416 mg L(-1); Al(3+) 0.037-1.875 mg L(-1), and Cu(2+)0.006-0.144 mg L(-1). The concentrations of most of the investigated parameters exceeded the recommended limit of the South African Guidelines and World Health Organization tolerance limits for freshwater quality. We conclude that these water bodies are potentially hazardous to public health and this highlights the need for implementation of improved management strategies of these river catchments for continued sustainability.