Nerella, Ashok; Jeripothula, Madhukar published the artcile< Design, synthesis and biological evaluation of novel deoxyvasicinone-indole as multi-target agents for Alzheimer's disease>, Synthetic Route of 399-76-8, the main research area is oxo tetrahydropyrroloquinazolinyl heteroaryl carboxamide preparation cholinesterase inhibitor mol docking; Acetylcholinesterase inhibitors; Alzheimer’s disease; Deoxyvasicinone; Indole; Multi target agents.
A series of multifunctional hybrids I [R = 1H-indol-2-yl, 1-benzofuran-2-yl, 1-benzothiophen-2-yl, etc.; R1 = H, Me] against Alzheimer’s disease were designed and obtained by conjugating the pharmacophores of deoxyvasicinone and indole. These analogs of deoxyvasicinone-indole were evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and as inhibitors of amyloid aggregation (Aβ1-42) for treatment of Alzheimer’s disease (AD). Subsequently, AChE induced Aβ aggregation inhibition test was also performed for selected compounds Biol. activity results demonstrated that compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] was the most potent and balanced dual ChEs inhibitor with IC50 values 0.12μM and 0.15μM for eeAChE and eqBuChE, resp. Kinetic anal. and docking study indicated that compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] was a mixed-type inhibitor for both AChE and BuChE. Compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] also found to be the best inhibitors of self-induced Aβ1-42 aggregation with IC50 values of 1.21μM. Compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] also afforded excellent inhibition of AChE-induced Aβ1-42 aggregation by 81.1%. Overall, these results indicate that I [R = 5-methoxy-1H-indol-2-yl, R1 = H] may be considered as lead compound for the development of highly effective anti-AD drugs.
Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Synthetic Route of 399-76-8.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles