Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis.

In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure-activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound 31 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate. Twenty-one bisbenzoxazole derivatives have been designed synthesized and evaluated to be an antiproliferative activity against four human tumor cell lines.

An efficient synthesis of novel di-heterocyclic benzazole derivatives and evaluation of their antiproliferative activities.

A series of unsymmetrical nine di-heterocyclic compounds of benzazole derivatives were synthesized at one step via cyclization reaction. The compounds evaluated for in vitro cytotoxic activity against A549, A498, HeLa, and HepG2 cancer cell lines. The biological evaluation results show that 23, 26 and 29 exhibit better activity against HepG2 and HeLa cancer cell lines. Compound 23 also showed good activity against A549, and A498 cancer cell lines. The analogs were further performed molecular docking studies against human cytochrome P450 2C8 monooxygenase enzyme, calculated some theoretical quantum parameters, ADMET descriptor and molecular electrostatic potential analysis. The strategy applied in this research work may act as a perspective for the rational design of potential anticancer drugs. Communicated by Ramaswamy H. Sarma.

New-Generation Benzimidazole-Based Plasmid Delivery Reagents with High Transfection Efficiencies on the Mammalian Cells.

Gene transfer and gene therapy studies require high-efficiency gene delivery reagents. By transferring the piece of DNA that we are interested in, we can alter the expression of certain gene or genes to further characterize its role in the cell function or in the organism's development, metabolism, immune system, etc. Transfection reagents that enable efficient delivery of the DNA to the cells are important tools in the molecular and cellular biology studies. There are chemical products and tools that have been used for transfection of the cells but they are not as efficient as desired or they can induce cytotoxicity. It is crucial to design and generate new transfection reagents to further support the field of biotechnology, molecular studies, cellular biology, and in vitro studies relying on them. The more efficient and the less cytotoxic compounds will be especially useful for the field. We synthesized a new set of benzimidazole-based transfection reagents that have higher efficiency to carry GFP expressing plasmid in to the mammalian cells compared with the commercially available ones with low cytotoxicity. GFP expression levels were tracked by flow cytometry to determine the transfection efficiencies. Benzimidazole-based transfection reagents can be safely used for transfection studies in tissue culture as well as in gene therapy applications due to their high efficiency in the gene transfer to the mammalian cells.

Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729µM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound.