ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Recent advances (2021–2023) in indole heterocycles, docking studies based anti-Alzheimer's agents

Phoebe F. Lamie, Mohamed A. Abdelgawad, and John N. Philoppes

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

E-mail: dr.feby@pharm.bsu.edu.eg

Received: 20 March 2026  Accepted: 24 May 2026

Abstract:

Alzheimer’s disease (AD) is a gradually worsening and incurable condition that affects the brain’s nerve cells with a complex, multifactorial origin, currently impacting over 30 million individuals worldwide. It is primarily characterized by memory impairment, cognitive deterioration, and behavioral disturbances, including emotional instability, depression, and increased motor activity. AD exists in two forms: an early-onset hereditary type and a late-onset sporadic form. Indole-based compounds have gained interest due to their inflammation -reducing and brain-protective properties, showing promise in mitigating AD-related damage. The development and advancement of AD are influenced by multiple factors and pathological mechanisms, including reduced acetylcholine (ACh) levels, buildup of amyloid-beta (Aβ) plaques and the formation of neurofibrillary tangles, synaptic dysfunction, brain inflammation, oxidative stress, and various lifestyle and metabolic contributors. This review emphasizes the recent advancements in the use of indole, bis-indole, and fused indole derivatives as multi-target compounds for the management of AD. Various mechanisms via which these compounds may inhibit the progression of AD are discussed. Indole-based derivatives shown considerable promise in alleviating the neurodegenerative effects associated with AD. Given the complex and multifactorial nature of AD, the multi-target-directed ligands (MTDLs) framework is regarded as one of the most promising therapeutic options. Within this framework, indole, bis-indole, and fused indole compounds have gained attention as particularly effective agents that act on multiple targets for treatment of AD.

Keywords: Alzheimer’s disease; Mental health; Biological markers; Indole; Choline esterase; Beta-amyloid; Tau-phosphorylation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-05112-w

Chemical Papers 80 (11) 12651–12669 (2026)