15315-50-1Relevant academic research and scientific papers
Design, synthesis, anticancer activity, and solid lipid nanoparticle formulation of indole-and benzimidazole-based compounds as pro-apoptotic agents targeting bcl-2 protein
Nagy, Manar I.,Darwish, Khaled M.,Kishk, Safaa M.,Tantawy, Mohamed A.,Nasr, Ali M.,Qushawy, Mona,Swidan, Shady A.,Mostafa, Samia M.,Salama, Ismail
, p. 1 - 37 (2021/02/16)
Cancer is a multifactorial disease necessitating identification of novel targets for its treat-ment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole-and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 μM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 μM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3,-8, and-9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.
Design, synthesis and QSAR study of arylidene indoles as anti-platelet aggregation inhibitors
Mirfazli, Seyedeh Sara,Khoshneviszadeh, Mehdi,Jeiroudi, Mohammad,Foroumadi, Alireza,Kobarfard, Farzad,Shafiee, Abbas
, p. 1 - 18 (2016/01/25)
A series of novel substituted indole carbohydrazide was synthesized and evaluated for anti-platelet aggregation activity. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis and were evaluated for their ability to inhibit platelet aggregation induced by adenosine diphosphate, arachidonic acid (AA) and collagen. Compounds 3e and 3b exhibited the highest activities against the platelet aggregation induced by collagen with IC50 values of 12.7 and 13.3 μM, respectively, and 2h with IC50 value of 51.88 μM and 2i with IC50 of 44.38 μM efficiently inhibited platelet aggregation induced by AA. The QSAR investigation indicated the importance of the topological, constitutional and geometrical parameters (PW3, PW4, LP1 and GATS6v) in describing the anti-platelet aggregation activity of the synthesized hydrazides. Evaluation of cytotoxic activity of the compounds against L929 cell line and three cancer cell lines revealed that none of the compounds have significant cytotoxicity. Graphical Abstract: [Figure not available: see fulltext.]
Salicylaldehyde-indole-2-acylhydrazone: A simple, colorimetric and absorption ratiometric chemosensor for acetate ion
Bao, Xiao-Ping,Zheng, Peng-Cheng,Liu, Yong,Tan, Zan,Zhou, Yu-Hui,Song, Bao-An
, p. 246 - 253 (2013/04/24)
A simple anion receptor (i.e. salicylaldehyde-indole-2-acylhydrazone) was synthesised and its recognition properties were investigated by naked-eye observation, UV-vis titration spectra, 1H NMR spectroscopy and DFT calculations. The obtained results indicated that this receptor could realise the selective colorimetric sensing and absorption ratiometric response towards AcO- in CH3CN-DMSO medium, by virtue of threefold intermolecular hydrogen bonding interactions formed with phenolic OH, indole NH and amide NH.
