23782-37-8Relevant articles and documents
Molecular structure investigation and tautomerism aspects of (E)-3-benzylideneindolin-2-one
Barakat, Assem,Al-Majid, Abdullah Mohammed,Islam, Mohammad Shahidul,Ali,Soliman, Saied M.,Siddiqui, Mohammed Rafiq Hussain,Ghabbour, Hazem A.,Fun, Hoong-Kun
, p. 1547 - 1556 (2015)
The synthesis and spectral characterization of the (E)-3-benzylideneindolin-2-one is reported. The compound crystallized in the monoclinic system with space group P21/n with cell coordinates a= 3.9849 (2) ?, b= 22.2236 (9) ?, c= 12.2501 (5) ?, β= 95.0535 (12) °, V=1080.64 (8) ? 3, and Z= 4. In the crystal, molecules are packed in chains formed via weak intermolecular C13-H13A ...O1 and N1-H1N1 ... O1 hydrogen bonding. The relative stabilities of the two tautomeric isomers of 3 are calculated by DFT/B3LYP method using 6-311G(d,p) basis set in gas phase and in solution. The quantum chemical calculations, NMR studies and the XRD analyses showed that the keto form T0 is the only form that could exist in gas, solution and solid phases respectively. The calculated geometric parameters of the dimer molecule showed better agreement with the XRD data than those obtained for single isolated molecule. This shed light on the effect of intermolecular interactions on the calculated geometric parameters. MEP study showed that, the O-atom and the NH proton are the most reactive H-acceptor and H-donor sites, respectively. The N-H.O H-bonding interactions increased the negative charge at the O-atoms and the positive charge of the NH protons compared to the monomer unit.
Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents
Ali, Abuzer,Devaraji, Vinod,Dewangan, Rikeshwer Prasad,Haider, Kashif,Pandey, Vivek,Pathak, Ankita,Raj Pokharel, Yuba,Saad, Suma,Shahar Yar, M.,Siddiqui, Nadeem
, (2021/09/22)
Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 μM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2–100 μM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.
3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis
Luczywo, Ayelen,González, Lucía G.,Aguiar, Anna C. C.,Oliveira de Souza, Juliana,Souza, Guilherme E.,Oliva, Glaucius,Aguilar, Luis F.,Casal, Juan J.,Guido, Rafael V. C.,Asís, Silvia E.,Mellado, Marco
supporting information, (2021/03/18)
Malaria is an infectious illness, affecting vulnerable populations in Third World countries. Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. So, eighteen oxindole derivatives, aza analogues were obtained with moderate to excellent yields. Also, the saturated derivatives of oxindole and aza derivatives via H2/Pd/C reduction were obtained in good yields, leading to racemic mixtures of each compound. Next, the inhibitory activity against P. falciparum of 18 compounds were tested, founding six compounds with IC50 20 μM. The most active of these compounds was 8c; however, their unsaturated derivative 7c was inactive. Then, a structure-activity relationship analysis was done, founding that focused LUMO lobe on the specific molecular zone is related to inhibitory activity against P. falciparum. Finally, we found a potential inhibition of lactate dehydrogenase by oxindole derivatives, using molecular docking virtual screening.
