An insight into the neuroprotective effects and molecular targets of pomegranate (Punica granatum) against Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD.Highlights An overview of traditional and pharmacological uses of pomegranate (POM).Potential of POM in the treatment of neurodegenerative diseases especially in AD.Insight into the molecular mechanisms of neuroprotective effects of POM in AD.Clinical evaluation studies involving POM and its bioactive components.

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

Alzheimer's disease (AD) is a neurological disorder that leads to dementia i.e., progressive memory loss accompanied with worsening of thinking ability of an individual. The cause of AD is not fully understood but it progresses with age where brain cells gradually die over time. According to the World Health Organization (WHO), currently 50 million people worldwide are affected by dementia and 60-70% of the cases belong to AD. Cumulative research over the past few decades have shown that molecules that act at a single target possess limited efficacy since these investigational drugs are not able to act against complex pathologies and thus do not provide permanent cure. Designing of multi-target directed ligands (MTDLs) appears to be more beneficial and a rational approach to treat chronic complex diseases including neurodegenerative diseases. Recently, MTDLs are being extensively researched by the medicinal chemists for the development of drugs for the treatment of various multifactorial diseases. Indole is one of the privileged scaffolds which is considered as an essential mediator between the gut-brain axis because of its neuroprotective, anti-inflammatory, ß-amyloid anti-aggregation and antioxidant activities. Herein, we have reviewed the potential of some indole-hybrids acting at multiple targets in the pathogenesis of AD. We have reviewed research articles from the year 2014-2021 from various scientific databases and highlighted the synthetic strategies, mechanisms of neuroprotection, toxicity, structure activity relationships and molecular docking studies of various indole-hybrid derivatives. This literature review of published data on indole derivatives indicated that developing indole hybrids have improved the pharmacokinetic profile with lower toxicity, provided synergistic effect, helped to develop more potent compounds and prevented drug-drug interactions. It is evident that this class of compounds have potential to inhibit multiple enzymes targets involved in the pathogenesis of AD and therefore indole hybrids as MTDLs may play an important role in the development of anti-AD molecules.

Chemistry and Pharmacological Activities of Biginelli Product- A Brief Overview.

Dihydropyrimidinones are extremely advantageous small sized molecules owning adaptable pharmaceutical properties. With a molecular formula C4H6N2O, they hold a wide range of biological activities. It is a heterocyclic moiety having two N-atoms at positions 1 and 3. They are derivatives of pyrimidine containing an additional ketone group. They have inspired development of a wide range of synthetic methods for preparation and chemical transformations. Taking into consideration their structural similarity and involvement with DNA and RNA, they have become very imperative in the world of synthetic organic chemistry. Aryl substituted moieties and their derivatives are significant class of substances in medicinal and organic chemistry. Many alkaloids from natural marine sources comprising dihydropyrimidinones core have been isolated which possess fascinating biological properties. Intensive explorations have been carried out on these compounds because they possess close similitude to clinically used nifedipine, nicardipine etc. which are also Biginelli product analogues. Due to the interesting pharmacological properties associated with the privileged DHPM structures, the Biginelli reaction and related procedures have received increasing attention in recent years.