7466-99-1Relevant articles and documents
Novel stilbene scaffolds efficiently targetMycobacterium tuberculosisnucleoid-associated protein, HU
Peraman, Ramalingam,Meka, Geethavani,Chilamakuru, Naresh Babu,Kutagulla, Vinay Kumar,Malla, Saloni,Ashby, Charles R.,Tiwari, Amit K.,Yiragamreddy, Padmanabha Reddy
, p. 10683 - 10692 (2021/06/27)
Novel scaffolds of stilbene were identified as inhibitors ofMycobacterium tuberculosisby targeting the nucleoid-associated protein, HU, using molecular docking. Based on the proposed combinatorial libraries I to VI, structures I and III had significantly greater docking binding energy that was comparable to that of the reference ligand, protein HU, fromMycobacterium tuberculosis.Using these docking results, 18 compounds were synthesized, characterized and evaluated forin vitroantitubercular (anti-TB) efficacy in theMycobacterium tuberculosisstrain, H37Rv. Thein vitroscreening results indicated a significant positive correlation between the docking binding efficacy (r2> 0.5) and clogp. Compounds3f,3dand4fwere ranked as top scoring ligands that interacted with amino acids ARG 53, ARG 55, PRO 81, PHE 79, and LYS 13, where the -NO2or -Cl substitution at theparaposition of the 3-phenyl ring was essential for interacting of the HU protein. The hydrogen bonding with ARG 55 and LYS 13 of these compounds was similar to that with the reference ligand that inhibits the HUMtbprotein. Compounds3d,3f, and4fwere evaluated as active leads, with MIC90 values of 21.3, 23.2 and 44.1 μM, respectively. The above mentioned compounds were also evaluated for antibacterial and antifungal efficacy in a panel of selected bacteria and fungi. Compound3dhad efficacy (MIC90: 6.82 μM) inS. aureusandE. coli. Compound3fwas also efficacious inE. coliandA. Niger, with an MIC90 value of 7.42 μM for both microorganisms. The fluoro-phenyl derivatives,3iand4i, were efficacious inC. albicans(MIC90 values of 8.2 and 7.8 μM, respectively) andA. niger(MIC90 values of 4.1 and 3.1 μM, respectively). Our results suggest that substitutions at theparaposition of 3-phenyl acryl derivatives with -NO2and -Cl significantly affected the binding interactions with the HUMtb protein in the docking studies. Furthermore these compounds had antitubercular and antimicrobial efficacy. The substituted phenyl acrylic acid and hydrazides could be inhibitors of the HUMtb protein ofMycobacterium tuberculosis.
INHIBITORS OF THE N-TERMINAL DOMAIN OF THE ANDROGEN RECEPTOR
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Page/Page column 53; 63; 64, (2018/08/12)
The present disclosure provides compounds and methods for inhibiting or degrading the N-terminal domain of the androgen receptor, as well as methods for treating cancers such as prostate cancer.
Further insights into the SAR of α-substituted cyclopropylamine derivatives as inhibitors of histone demethylase KDM1A
Pieroni, Marco,Annunziato, Giannamaria,Azzali, Elisa,Dessanti, Paola,Mercurio, Ciro,Meroni, Giuseppe,Trifiró, Paolo,Vianello, Paola,Villa, Manuela,Beato, Claudia,Varasi, Mario,Costantino, Gabriele
, p. 377 - 386 (2015/03/05)
Epigenetics alterations including histone methylation and acetylation, and DNA methylation, are thought to play important roles in the onset and progression of cancer in numerous tumour cell lines. Lysinespecific demethylase 1 (LSD1 or KDM1A) is highly ex
