Convenient Synthesis and Anticancer Activity of Methyl 2-[3-(3-Phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and N-Alkyl 3-((3-Phenyl-quinoxalin-2-yl)sulfanyl)propanamides

Abstract

A series of methyl 2-[3-(3-phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and their corresponding hydrazides and N-alkyl 3-((3-phenylquinoxalin-2-yl)sulfanyl)propanamides were prepared on the basis of the chemoselective Michael reaction of acrylic acid with the parent substrate 3-phenylquinoxaline-2(1H)-thione. The parent thione was produced by a convenient novel thiation method from the corresponding 3-phenylquinoxalin-2(1H)-one. The chemical structures of the newly synthesized compounds were confirmed by elemental analyses, 1H and 13C NMR. The antiproliferative activity of the synthesized compounds was tested against human HCT-116 and MCF-7 cell lines. Out of 25 screened derivatives, 10 active compounds exhibited IC50’s in the range 1.9–7.52 μg/mL on the HCT-116, and 17 active compounds exhibited IC50’s in the range 2.3–6.62 μg/mL on the MCF-7 cell lines compared to the reference drug doxorubicin (IC50 3.23 μg/mL). The structure–activity relationship of the tested compounds was studied through their binding affinity to the human thymidylate synthase allosteric site in silico using molecular docking and proved the quinoxaline ring as a suitable scaffold carrying a peptidomimetic side chain in position 3.

Newly synthesized 3-(4-chloro-phenyl)-3-hydroxy-2,2-dimethyl-propionic acid methyl ester derivatives selectively inhibit the proliferation of colon cancer cells

“…The cell culture and MTT assay was done as per previously described method. 39 However, we have described the method in brief. Cells were grown in 96-well plates in the culture media containing DMEM, L-glutamine, fetal bovine serum, selenium chloride and penicillin-streptomycin.…”

<p>Doxorubicin Delivered Using Nanoparticles Camouflaged with Mesenchymal Stem Cell Membranes to Treat Colon Cancer</p>

“…Then, the medium in the wells was replaced with 200 μL fresh medium containing free DOX, DOX-SPIO, or DOX-SPIO@MSCs, at different DOX concentrations, and the MC38 cells incubated for 48 h. Next, the cells were washed with PBS three times and incubated with DMEM supplemented with 10% CCK-8 for a further 2 h. Finally, optical density (OD) at 450 nm was measured using a Multi-mode microplate reader (TECAN, Switzerland). Cell viability was calculated using the following equation: 3 Cell viability % ð Þ¼ OD test sample=OD control  100%…”

“…When the MC38 xenograft tumor volumes increased to almost 250 mm 3 , tumor-bearing mice were intravenously injected with PBS, free DOX, DOX-SPIO, or DOX-SPIO @MSCs, at a DOX dosage of 10 mg/kg. Mice were sacrificed at 24 h post-injection and major organs (heart, liver, spleen, lung, kidney, and tumor) harvested for ex vivo imaging and semi-quantitative biodistribution analysis.…”

“…Nanocarriers based on targeted drug delivery systems have been extensively researched and rapidly developed for application in clinical oncology treatments. [1][2][3][4] To date, enhanced permeability and retention effects remain the primary mechanism of uptake of tumor-specific nanocarriers. 5 Most nanoparticles (NPs) are recognized by the immune system and cleared as foreign substances, thereby limiting their clinical application.…”

Synthesis, Molecular Docking and Biological Evaluation of Some New Benzotriazines

“…One of the most corner stone principles in our research group is based on searching for new anticancer drugs 1,2 where the search for new anticancer drugs is never ending task with the aim to obtain products with lower toxicity and more selectivity towards tumor cells. Benzotriazine and its derivatives possess a diverse range of biological activities of pharmacological activities including antimicrobial, 3 antiinflammatory 4 , anti-depressant 5 , anti-ulcer 6 , antidiarrhoeal 7 , anaesthetics 8 , anticancer 9 .…”