5812-07-7Relevant articles and documents
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.
Selective C3-alkenylation of oxindole with aldehydes using heterogeneous CeO2 catalyst
Rashed, Md. Nurnobi,Touchy, Abeda Sultana,Chaudhari, Chandan,Jeon, Jaewan,Siddiki, S.M.A. Hakim,Toyao, Takashi,Shimizu, Ken-ichi
, p. 970 - 976 (2020/01/31)
We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields (87%–99%) and high stereoselectivities (79%–93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction.
Investigation of triazole-linked indole and oxindole glycoconjugates as potential anticancer agents: Novel Akt/PKB signaling pathway inhibitors
Nagarsenkar, Atulya,Prajapti, Santosh Kumar,Guggilapu, Sravanthi Devi,Birineni, Swetha,Sravanti Kotapalli, Sudha,Ummanni, Ramesh,Babu, Bathini Nagendra
supporting information, p. 646 - 653 (2016/05/19)
In continuation of our venture towards the synthesis of novel bioactive agents, two sets of triazole-linked glycoconjugates were synthesized from indole/oxindole (29 compounds) and were further characterized by IR (infrared spectroscopy), 1H NM
