The Multi‐Pharmacological Targeted Role of Indole and its Derivatives: A review

ChemistrySelect, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 2, 2023

Abstract Heterocycles are a privileged motif that appears as momentous objective in medicinal chemistry. An important class of compounds for drug discovery and design is indole its derivatives, which have been examined variety biological activities. Therefore, it noteworthy the modern progress synthetic, chemistry; last decade has onlooker with multitude reports on several derivatives corroborating these chemical entities to be renowned target new drugs. The current study includes brief natural sources indole, range commercially available indole‐based Additionally, this review discusses numerous facets structure‐activity relationship (SARs) provides information about varied pharmacological effects derivatives. literature data presented anti‐pharmacological agents herein covers largely from year 2015 mid 2022.

Язык: Английский

---

Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents

Molecules, Год журнала: 2024, Номер 29(9), С. 2127 - 2127

Опубликована: Май 3, 2024

Neurodegeneration is a gradual decay process leading to the depletion of neurons in both central and peripheral nervous systems, ultimately resulting cognitive dysfunctions deterioration brain functions, alongside decline motor skills behavioral capabilities. Neurodegenerative disorders (NDs) impose substantial socio-economic strain on society, aggravated by advancing age world population absence effective remedies, predicting negative future. In this context, urgency discovering viable therapies critical and, despite significant efforts medicinal chemists developing potential drug candidates exploring various small molecules as therapeutics, regrettably, truly treatment yet be found. Nitrogen heterocyclic compounds, particularly those containing indole nucleus, which has emerged privileged scaffold, have attracted particular attention for variety pharmacological applications. This review analyzes rational design strategy adopted different research groups development anti-neurodegenerative indole-based compounds modulate molecular targets involved NDs, with reference most recent advances between 2018 2023.

Язык: Английский

---

Indole Derivatives: A Versatile Scaffold in Modern Drug Discovery—An Updated Review on Their Multifaceted Therapeutic Applications (2020–2024)

Molecules, Год журнала: 2024, Номер 29(19), С. 4770 - 4770

Опубликована: Окт. 9, 2024

Indole derivatives have become an important class of compounds in medicinal chemistry, recognized for their wide-ranging biological activities and therapeutic potential. This review provides a comprehensive overview recent advances the evaluation indole-based last five years, highlighting roles cancer treatment, infectious disease management, anti-inflammatory therapies, metabolic disorder interventions, neurodegenerative management. shown significant efficacy targeting diverse pathways, making them valuable scaffolds designing new drugs. Notably, these demonstrated ability to combat drug-resistant cells pathogens, breakthrough field, offer promising options chronic diseases such as diabetes hypertension. By summarizing key findings exploring underlying mechanisms, this underscores potential indole addressing major healthcare challenges, thereby instilling hope optimism field modern medicine.

Язык: Английский

---

Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases

Neurology International, Год журнала: 2025, Номер 17(2), С. 26 - 26

Опубликована: Фев. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Язык: Английский

---

Rational drug design strategies for the development of promising multi-target directed indole hybrids as Anti-Alzheimer agents

Bioorganic Chemistry, Год журнала: 2022, Номер 127, С. 105941 - 105941

Опубликована: Июнь 10, 2022

Язык: Английский

---

Research progress of natural products and their derivatives against Alzheimer’s disease

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2023, Номер 38(1)

Опубликована: Фев. 20, 2023

Alzheimer's disease (AD), a persistent neurological dysfunction, has an increasing prevalence with the aging of world and seriously threatens health elderly. Although there is currently no effective treatment for AD, researchers have not given up, are committed to exploring pathogenesis AD possible therapeutic drugs. Natural products attracted considerable attention owing their unique advantages. One molecule can interact multiple AD-related targets, thus having potential be developed in multi-target drug. In addition, they amenable structural modifications increase interaction decrease toxicity. Therefore, natural derivatives that ameliorate pathological changes should intensively extensively studied. This review mainly presents research on AD.

Язык: Английский

---

Design, synthesis, and biological evaluation of novel (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives as multifunctional agents for the treatment of Alzheimer's disease

European Journal of Medicinal Chemistry, Год журнала: 2021, Номер 227, С. 113973 - 113973

Опубликована: Ноя. 3, 2021

Язык: Английский

---

Synthesis and molecular docking simulation of new benzimidazole–thiazole hybrids as cholinesterase inhibitors

Archiv der Pharmazie, Год журнала: 2023, Номер 357(1)

Опубликована: Ноя. 8, 2023

Abstract Dementia is a cognitive disturbance that generally correlated with central nervous system diseases, especially Alzheimer's disease. The limited number of medications available insufficient to improve the lifestyle patients suffering from this Thus, new benzimidazole–thiazole hybrids ( 3–10 ) were designed and synthesized as acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibitory agents. in vitro evaluation displayed derivatives 4b , 4d 5b 6a 7a 8b demonstrated dual efficiency against both AChE IC 50 ranging 4.55 8.62 µM BChE 3.50 8.32 µM. By analyzing Lineweaver–Burk plot, an uncompetitive form inhibition was determined for highly active compound revealing its type. human telomerase reverse transcriptase‐immortalized retinal pigment epithelial cell line used ensure safety most potent cholinesterase inhibitors. Furthermore, compounds evaluated their neuroprotective antioxidant properties, well ability suppress COX‐2. results presented significant neuroprotection H 2 O ‐induced damage SH‐SY5Y cells % viability 67.42 ± 7.90%, 62.51 6.71%, 72.61 8.10%, respectively, while tested candidates did not reveal activity. Otherwise, outstanding COX‐2 effects 0.050 0.080 μM relative celecoxib (IC = µM). In addition, molecular docking carried out sites (PDB ID: 4EY7) code: 1P0P). fit portions, scores −8.65 −6.64 kcal/mol (for AChE) −8.71 −7.73 BChE). silico show have good physicochemical pharmacokinetic properties no Lipinski rule violations. preceding exhibited could be template developing more inhibitors future.

Язык: Английский

---

New Indole Derivatives As Multitarget anti-Alzheimer's Agents: synthesis, Biological Evaluation and Molecular Dynamics

Future Medicinal Chemistry, Год журнала: 2023, Номер 15(6), С. 473 - 495

Опубликована: Март 1, 2023

Background: Alzheimer's disease is a neurological disorder that causes brain cells to shrink and die. Aim: Thirteen novel 'oxathiolanyl', 'pyrazolyl' 'pyrimidinyl' indole derivatives were designed synthesized as anti-Alzheimer's treatment. Method:In vitro enzyme assay was performed against both AChE BChE enzymes. In addition, antioxidant cytotoxicity on normal cell line determined. Molecular docking dynamic simulations conducted confirm the binding mode in esterases' active sites. silico absorption, distribution, metabolism, excretion toxicity studies also carried out. Results & conclusion: Compounds 5, 7 11 exhibited superior inhibitory activity acetylcholinesterase butyrylcholinesterase, with IC50 values of 0.042 3.003 μM, 2.54 0.207 μM 0.052 2.529 respectively, compared donepezil.

Язык: Английский

---

Tryptamine: A privileged scaffold for the management of Alzheimer's disease

Drug Development Research, Год журнала: 2023, Номер 84(8), С. 1578 - 1594

Опубликована: Сен. 7, 2023

Abstract Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative associated with aging. It characterized by the progressive loss of memory other cognitive functions. Although exact etiology AD not well explored, several factors, such as deposition amyloid‐β (Aβ) plaques, hyperphosphorylation tau protein, presence low levels acetylcholine, generation oxidative stress, are key mediators in progression AD. Currently, clinical treatment options for limited based on cholinesterase (ChE) inhibitors (e.g., donepezil, rivastigmine, galantamine), N ‐methyl‐ d ‐aspartic acid receptor antagonists memantine), recently approved Aβ modulator aducanumab). Tryptamine (2‐(1 H ‐indol‐3‐yl)ethan‐1‐amine) small molecule that contains an indole nucleus ethylamine side chain. also active metabolite tryptophan. possesses wide range biological activities related to disorders, ChE inhibition, aggregation antioxidant effects, monoamine‐oxidase neuroprotection. Several tryptamine‐based hybrid analogs currently being investigated multifunctional agents development novel hybrids treatment. Thus, this review article aims provide in‐depth insights into research progress strategies designing used therapy.

Язык: Английский

---