Structure − Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on β ‑ Amyloid Aggregation Kinetics

Paper

Structure − Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on β ‑ Amyloid Aggregation Kinetics

Published 2016 · T. Mohamed, A. Shakeri, Gary Tin

UNKNOWN SJR score

20

Citations

0

Influential Citations

Semantic Scholar

Abstract

: A library of isomeric 2,4-diaminoquinazoline (DAQ) derivatives were synthesized and evaluated for antiaggregation potential toward A β 40/42. Structure − activity relationship data identi ﬁ ed compound 3k ( N 4 -(4-bromobenzyl)-quinazoline-2,4-diamine) with a 4-bromobenzyl substituent as the most potent inhibitor (A β 40 IC 50 = 80 nM) and was almost 18-fold more potent compared to the reference agent curcumin (A β 40 IC 50 = 1.5 μ M). The corresponding N 2 -isomer 4k ( N 2 -(4-bromobenzyl)quinazoline-2,4-diamine) was also able to prevent A β aggregation (A β 40 IC 50 = 1.7 μ M). However, compound 4k exhibited superior inhibition of A β 42 aggregation (A β 42 IC 50 = 1.7 μ M) compared to compound 3k (A β 42 IC 50 = 14.8 μ M) and was ∼ 1.8-fold more potent compared to curcumin (A β 42 IC 50 = 3.1 μ M). These results were supported by A β aggregation kinetics investigations and transmission electron microscopy studies, which demonstrate the suitability of DAQ ring system to develop antiamyloid agents as pharmacological tools to study A β aggregation.

In Vitro Study

Study Snapshot

Isomeric 2,4-diaminoquinazolines show potential as antiamyloid agents, with compound 3k being the most potent inhibitor of A40 aggregation and compound 4k showing superior inhibition of A42 aggregation compared to curcumin.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Structure − Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on β ‑ Amyloid Aggregation Kinetics

Sign up to use Study Snapshot

References

Citations

Exploring Quinazoline as a Scaffold for Developing Novel Therapeutics in Alzheimer’s Disease

Quinazoline derivatives show promising potential in developing novel anti-Alzheimer's disease drugs by targeting various pathologies and exhibiting drug-like aspects and pharmaceutical features.

Combined Experimental and Computational Investigations of 4‐Amino‐2‐Chloro‐6,7‐Dimethoxyquinazoline as Potential Anti‐Alzheimer Agent

ACDQ shows potential as an effective lead therapeutic for Alzheimer's disease, with strong interaction with 4EY7 protein and potential for ADMET prediction.

N-Benzyl, N-phenethyl and N-benzyloxybenzamide derivatives inhibit amyloid-beta (Aβ42) aggregation and mitigate Aβ42-induced neurotoxicity

N-benzylbenzamides 3a and 3f, N-phenethylbenzamide 5a, and N-benzyloxybenzamide 7a show promising anti-aggregation properties and mitigate A42-induced neurotoxicity, offering potential as Alzheimer's disease tools and therapeutics.

Design, Synthesis, and Neuroprotective Activity of Phenoxyindole Derivatives on Antiamyloid Beta (Aβ) Aggregation, Antiacetylcholinesterase, and Antioxidant Activities

Phenoxyindole derivatives show potential as new Alzheimer's disease therapeutic approaches due to their anti-A aggregation and antioxidant properties.

Design, synthesis and structure-activity relationship studies of 3-phenylpyrazino[1,2-a]indol-1(2H)-ones as amyloid aggregation and cholinesterase inhibitors with antioxidant activity

The lead compound 5i shows potential as a multi-targeted Alzheimer's disease agent by inhibiting amyloid aggregation, cholinesterase enzymes, and exhibiting antioxidant properties without toxicity.