5318-27-4Relevant articles and documents
Structure-based drug design, synthesis, In vitro, and In vivo biological evaluation of indole-based biomimetic analogs targeting estrogen receptor-α inhibition
Hendy, Moataz S.,Ali, Aya A.,Ahmed, Lubna,Hossam, Reham,Mostafa, Alaa,Elmazar, Mohamed M.,Naguib, Bassem H.,Attia, Yasmeen M.,Ahmed, Mahmoud Salama
, p. 281 - 290 (2019)
Offering novel scaffolds targeting estrogen receptor creates huge necessity to overcome the evolving resistance developed by tumors. Structure-based drug design coupled with ring opening strategy of the steroids skeleton revealed the potential of indole-based analogs to be synthesized targeting the ligand binding domain of estrogen receptor-α. In vitro studies revealed the potential of the total sub-classes of the synthesized analogs to show anti-proliferative activity against estrogen receptor-dependent cancer cell lines at IC50 ranging from 28.23 to 57.13 μM. This was further validated by evaluating the potential of the synthesized analogs to compete along with estradiol via ER-α ELISA assay to show inhibitory profile at IC50 ranging from 1.76 to 204.75 nM. Two analogs (YMA-005 and YMA-006) showed significant reduction in tumor size at two dose levels with extensive degeneration and necrosis. Both YMA-005 and YMA-006 showed in-situ reduction of ER-α Immunohistochemical expression at both dose levels. Ultimately, novel analogs of indole-based biomimetic of estrone scaffolds were offered as estrogen receptor-α inhibitors.
COPPER NANOPARTICLE BASED CHEMOSELECTIVE REDUCTION
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Paragraph 0050; 0051, (2021/11/20)
The instant invention provides processes for a chemo selective reduction of a nitro group within a compound in the presence of other groups which can also be reduced. This aspect of the present invention provides an ammonia borane (AB) initiated chemoselective reduction process of a nitro group contained within a compound in the presence of a copper (Cu) nanoparticle based catalyst. The invention is also directed to Copper (Cu) nanoparticle (NP) based catalysts, selected from Cu/WOx, Cu/SiO2, and Cu/C; wherein x represents an integer having a value of from about 2 to about 3.5, used in the chemo selective reduction of a nitro group contained within a compound in the presence of other groups which can also be reduced.
Flexible Versus Rigid G-Quadruplex DNA Ligands: Synthesis of Two Series of Bis-indole Derivatives and Comparison of Their Interactions with G-Quadruplex DNA
Prasad, Bagineni,Jamroskovic, Jan,Bhowmik, Sudipta,Kumar, Rajendra,Romell, Tajanena,Sabouri, Nasim,Chorell, Erik
supporting information, p. 7926 - 7938 (2018/06/15)
Small molecules that target G-quadruplex (G4) DNA structures are not only valuable to study G4 biology but also for their potential as therapeutics. This work centers around how different design features of small molecules can affect the interactions with G4 DNA structures, exemplified by the development of synthetic methods to bis-indole scaffolds. Our synthesized series of bis-indole scaffolds are structurally very similar but differ greatly in the flexibility of their core structures. The flexibility of the molecules proved to be an advantage compared to locking the compounds in the presumed bioactive G4 conformation. The flexible derivatives demonstrated similar or even improved G4 binding and stabilization in several orthogonal assays even though their entropic penalty of binding is higher. In addition, molecular dynamics simulations with the c-MYC G4 structure showed that the flexible compounds adapt better to the surrounding. This was reflected by an increased number of both stacking and polar interactions with both the residues in the G4 DNA structure and the DNA residues just upstream of the G4 structure.
