Current Issue : July - September Volume : 2020 Issue Number : 3 Articles : 6 Articles
Cancer is a leading cause of death worldwide. Multidrug resistance (MDR) is a main reason\nof chemotherapy failure in many patients and is often related to overexpression of ATP-binding\ncassette (ABC) transporters, including P-glycoprotein (P-gp/ABCB1). Agents that are capable of\nmodulation of the activity of these transporters might be effective in overcoming MDR. In this study, a\nnew set of 1,4,5,6,7,8-hexahydro 5-oxo quinoline-3-carboxamide derivatives bearing 4-methylthiazole\nmoiety and their tetrahydroquinoline counterparts were synthesized. MDR reversal activity of\nthese 16 newly synthesized derivatives was tested in P-gp overexpressing MES-SA-DX5 human\nuterine sarcoma cells by flow cytometric determination of Rhodamine123 efflux. The effect of the\nmost potent compounds in induction of apoptosis and alterations of cell cycle was examined in\nthese cells by a flow cytometric method. Inherent cytotoxicity of the synthesized compounds was\nevaluated against MCF-7, A-549 and K562 cancer cell lines, as well as MES-SA-DX5 and their parental\nnon-resistant MES-SA and also HEK-293 non-cancerous cells by MTT assay. Compounds A1 and A2\nwith 5-oxo-hexahydroquinoline structure bearing 2,4-dichlorophenyl and 4-bromophenyl moieties,\nrespectively, and their tetrahydroquinoline counterparts B1 and B2 significantly blocked P-gp efflux,\ninduced apoptosis and showed the highest cytotoxicities against MES-SA-DX5 cells. However,\nonly A2 and B2 compounds were relatively selective against cancer and MDR cells as compared to\nnon-resistant and non-cancerous cells. These findings demonstrate that 5-oxo-hexahydroquinoline\nand 5-oxo-tetrahydroquinoline derivatives represent promising agents with therapeutic potential in\ndrug resistant cancers....
Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosquitoes. According to the WHO\nreport of 2015, there were 214 million cases of malaria with 438,000 deaths worldwide. Ninety percent of worldâ??s malaria cases occur\nin Africa, where the disease is recognized as a serious impediment to economic and social development. Despite advancement in\nmalaria research, the disease continues to be a global problem, especially in developing countries. Currently, there is no effective\nvaccine for malaria control. In addition, although there are effective drugs for treatment of malaria, this could be lost to the drug\nresistance in different Plasmodium species. The most lethal form is caused by P. falciparum which has developed resistance to many\nchemotherapeutic agents and possibly to the current drugs of choice. Reducing the impact of malaria is a key to achieving the\nsustainable development goals which are geared toward combating the disease. Covalent bitherapy is a rational and logical way of\ndrug design which entails joining a couple of molecules with individual intrinsic action into a unique agent, hence packaging dual\nactivity into one hybrid. This suggests the need to develop new antimalarial drugs that are effective against malaria parasites based on\nthe new mode of action, molecular targets, and chemical structures. In silico studies have shown that sarcosine is able to bind to\nunique plasmodia proteins (P. falciparum ATCase), whereas aniline can be a ligand to target protein (enoyl acyl carrier protein\nreductase), hence suppressing the progression of the disease. The main objective of this study was to synthesize and determine the\nefficacy and safety of antiplasmodial hybrid drug comprising the sarcosine and aniline derivative......................
Four indole-3-carbaldehyde semicarbazone derivatives, 2-((5-bromo-1H-indol-3-yl)methylene)hydrazinecarboxamide (1), 2-((5-\nchloro-1H-indol-3-yl)methylene)hydrazinecarboxamide (2), 2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinecarboxamide (3), and\n2-((4-nitro-1H-indol-3-yl)methylene)hydrazinecarboxamide (4) were synthesized and characterized by ESI-MS and spectroscopic (FTIR,\n1HNMR, and 13C NMR) techniques.The two-dimensionalNMR(in acetone-d6) spectral data revealed that the molecules 1 and 2 in\nsolution are in the cisE isomeric form. This evidence is supported by DFTcalculations at the B3LYP/6-311++G(d,p) level of theory where\nit was shown that the corresponding most stable conformers of the synthesized compounds have a cisE geometrical configuration, in\nboth the gas and liquid (acetone and DMSO) phases.Thein vitro antibacterial activity of compounds 1â??4 was determined against Grampositive\n(Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria.\nAmong all the tested semicarbazones, 1 and 2 exhibited similar inhibitory activities against Staphylococcus aureus....................
A series of coumarin Schiff bases, (E)-N’arylidine-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-acetohydrazides (IVa-m) were synthesized by the reaction of intermediate, acetohydrazide of coumarin(III) with different aryl/hetero aromatic aldehydes in chloroform:methanol (1:1) mixture, in presence of glacial acetic acid and characterized by IR, NMR and Mass spectral data. The title compounds were evaluated for in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv by almar blue dye method and in-vitro antimicrobial activity against bacterial strains by serial dilution method. All the compounds exhibited moderate to weak antitubercular activity and compound IVe with 1, 2-dioxymethylene substitution on phenyl ring exhibited excellent antibacterial activity and compound IVh with p-nitro substitution on phenyl ring exhibited good antibacterial activity while other compounds displayed moderate to weak antibacterial activity against Gram positive bacteria S. aureus when compared with standard drug. None of the compounds were able to exhibit the antibacterial activity against Gram negative bacteria E. coli with MIC value of 100 µg/ml or more. In conclusion, our study has successfully identified potent antibacterial activity of coumarin schiff bases....
Chrysin is a naturally occurring flavonoid with mild anticancer activity. In this paper\nwe report the synthesis of new chrysin derivatives alkylated with N-phenylchloroacetamides in\nposition 7. A novel method was developed for the preparation of 7-aminochrysin derivatives via\nthe Smiles rearrangement, resulting in diphenylamine-type compounds. In silico studies of the\nSmiles rearrangement were performed. We also present the in vitro antiproliferative activity of the\nsynthesized compounds against 60 human tumor cell lines (NCI60). The most potent derivative\nexhibited nanomolar antitumor activity on the MCF7 cell line of breast cancer (GI50 = 30 nM) and on\nthe HCT-15 cell line of colon cancer (GI50 = 60 nM)....
Squalene (SQ), a natural precursor of many steroids, can inhibit tumor progression and decrease serum cholesterol levels.\nHowever, it is difficult to discern the effect of highly active molecules in the treatment of diseases because not enough active\ncompounds reach the site of pathology in crowded biosystems. 2erefore, it is necessary to design artificial probes that work\neffectively within crowded systems. In this study, to facilitate cell penetration, the ethylene glycol moiety (used as a probe) was\nchemically added to SQ to form 2-(2-hydroxyethoxy)-3-hydroxysqualene (HEHSQ). HEHSQ was prepared from 2,3-epoxysqualene\nand characterized by Rf, FT-IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry. We then evaluated the\nanti-inflammatory effects of SQ and HEHSQ on lipopolysaccharide- (LPS-) stimulated RAW264.7 murine macrophages. To\ndetermine the effect of SQ and HEHSQ on the viability of RAW264.7 cells, an MTT assay was performed. To quantify the antiinflammatory\neffect of SQ and HEHSQ, we measured nitric oxide (NO) production, gene expression, and secretion of the\nproinflammatory cytokine tumor necrosis factor..........................
Loading....