Evaluation of Anti-Alzheimer's Potential of Azo-Stilbene-Thioflavin-T derived Multifunctional Molecules: Synthesis, Metal and Aβ Species Binding and Cholinesterase Activity.

Inhibition of amyloid β (Aβ) aggregation and cholinesterase activity are two major therapeutic targets for Alzheimer's disease (AD). Multifunctional Molecules (MFMs) specifically designed to address other contributing factors, such as metal ion induced abnormalities, oxidative stress, toxic Aβ aggregates etc. are very much required.

Exploring malaria parasite surface proteins to devise highly immunogenic multi-epitope subunit vaccine for Plasmodium falciparum.

Background: Malaria has remained a major health concern for decades among people living in tropical and sub-tropical countries. Plasmodium falciparum is one of the critical species that cause severe malaria and is responsible for major mortality. Moreover, the parasite has generated resistance against all WHO recommended drugs and therapies.

Structure-based virtual screening against multiple Plasmodium falciparum kinases reveals antimalarial compounds.

The continuous emergence of resistance against most frontline antimalarial drugs has led to countless deaths in malaria-endemic countries, counting 619,000 deaths in 2021, with mutation in drug targets being the sole cause. As mutation is correlated frequently with fitness cost, the likelihood of mutation emergence in multiple targets at a time is extremely low. Hence, multitargeting compounds may seem promising to address drug resistance issues with additional benefits like increased efficacy, improved safety profile, and the requirement of fewer pills compared to traditional single and combinational drugs.

Malaria therapeutics: are we close enough?

Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of socioeconomic losses in developing countries. WHO approved several antimalarials in the last 2 decades, but the growing resistance against the available drugs has worsened the scenario.

Drug repurposing based novel anti-leishmanial drug screening using and approaches.

Visceral leishmaniasis is a neglected tropical disease and is mainly caused by in the Indian subcontinent. The mitochondria genome replication in is having a very specific mechanism, and it is initiated by a key enzyme called mitochondrial primase. This enzyme is essential for the onset of the replication process and growth of the parasite.

Synthesis and inhibition studies towards the discovery of benzodiazepines as potential antimalarial compounds.

The target-based discovery of therapeutics against apicoplast, an all-important organelle is an overriding perspective. MEP pathway, an accredited drug target provides an insight into the importance of apicoplast in the survival of the parasite. In this study, we present the rational design strategy employing sustainable catalysis for the synthesis of benzodiazepine (BDZ) conformers followed by their biological evaluation as prospective inhibitors against the potential target of the IPP pathway, 1-deoxy-D-xylulose-5-phosphatereductoisomerase (DXR).

Azo-Stilbene and Pyridine-Amine Hybrid Multifunctional Molecules to Target Metal-Mediated Neurotoxicity and Amyloid-β Aggregation in Alzheimer's Disease.

Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with progressive neuronal cell death, and they are commonly correlated with aberrant protein misfolding and aggregation of Aβ peptides. Transition metal ions (Cu, Fe, and Zn) have been shown to promote aggregation and oxidative stress through formation of Aβ-metal complexes. In this context, integrating molecular scaffolds rationally is used here to generate multifunctional molecules as modulators for metal-induced abnormalities.

Aryldiazoquinoline based multifunctional small molecules for modulating Aβ aggregation and cholinesterase activity related to Alzheimer's disease.

Research continues to find a breakthrough for the treatment of Alzheimer's Disease (AD) due to its complicated pathology. Presented herein is a novel series of arydiazoquinoline molecules investigated for their multifunctional properties against the factors contributing to Alzheimer's disease (AD). The inhibitory properties of fourteen closely related aryldiazoquinoline derivatives have been evaluated for their inhibitory effect on Aβ peptide aggregation.

Development of multi-epitope driven subunit vaccine in secretory and membrane protein of Plasmodium falciparum to convey protection against malaria infection.

Malaria infection is the severe health concern for a long time. As per the WHO reports, the malarial infection causes huge mortality all around the world and is incomparable with any other infectious diseases. The absence of effective treatment options and increasing drug resistance to the available therapeutics like artemisinin and other derivatives demand an efficient alternative to overcome this death burden.

Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase.

The emergence of mutations leading to drug resistance is the main cause of therapeutic failure in the human HIV infection. Chemical system biology approach has drawn great attention to discover new antiretroviral hits with high efficacy and negligible toxicity, which can be used as a prerequisite for HIV drug resistance global action plan 2017-21. To discover potential hits, we docked 49 antiretroviral analogs (n = 6294) against HIV-1 reverse transcriptase Q151M mutant & its wild-type form and narrow downed their number in three sequential modes of docking using Schrödinger suite.

Author Correction: Genome-wide identification and expression analysis of E2 ubiquitin-conjugating enzymes in tomato.

A correction has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein.

Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response.

Relict plastidic metabolic process as a potential therapeutic target.

The alignment of the evolutionary history of parasites with that of plants provides a different panorama in the drug development process. The housing of different metabolic processes, essential for parasite survival, adds to the indispensability of the apicoplast. The different pathways responsible for fueling the apicoplast and parasite offer a myriad of proteins responsible for the apicoplast function.

Genome-wide identification and expression analysis of E2 ubiquitin-conjugating enzymes in tomato.

The ubiquitin-proteasomal degradation mechanism has gained the attention over the past decade. The E2 ubiquitin conjugating enzymes are the crucial part of ubiquitination mechanism and they are believed to hold imperative association for plant development. It accepts ubiquitin from the E1 enzyme and interacts with the E3 ligase to transfer ubiquitin or directly transfers ubiquitin to the substrate.

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage.

Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis.

Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling.

Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P.

High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania.

Visceral leishmaniasis (VL) has been considered as one of the most fatal form of leishmaniasis which affects 70 countries worldwide. Increased drug resistance in Indian subcontinent urged the need of new antileishmanial compounds with high efficacy and negligible toxicity. Imipramine compounds have shown impressive antileishmanial activity.

Cancer/testis antigens as molecular drug targets using network pharmacology.

Present chemotherapeutic drugs have limited efficacy and severe side effects. Considering the complexity of cancer, an effective strategy is necessary to discover multiple new drug targets. Cancer/testis antigens are vital for cancer cell progression.

In-silico studies on DegP protein of Plasmodium falciparum in search of anti-malarials.

Despite encouraging progress over the past decade, malaria caused by the Plasmodium parasite continues to pose an enormous disease burden and is one of the major global health problems. The extreme challenge in malaria management is the resistance of parasites to traditional monochemotherapies like chloroquine and sulfadoxine-pyrimethamine. No vaccine is yet in sight, and the foregoing effective drugs are also losing ground against the disease due to the resistivity of parasites.

Role of Ubiquitin-Mediated Degradation System in Plant Biology.

Ubiquitin-mediated proteasomal degradation is an important mechanism to control protein load in the cells. Ubiquitin binds to a protein on lysine residue and usually promotes its degradation through 26S proteasome system. Abnormal proteins and regulators of many processes, are targeted for degradation by the ubiquitin-proteasome system.

Recent Updates on DTD (D-Tyr-tRNA(Tyr) Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis.

During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell.

Plasmodium falciparum Secretome in Erythrocyte and Beyond.

Plasmodium falciparum is the causative agent of deadly malaria disease. It is an intracellular eukaryote and completes its multi-stage life cycle spanning the two hosts viz, mosquito and human. In order to habituate within host environment, parasite conform several strategies to evade host immune responses such as surface antigen polymorphism or modulation of host immune system and it is mediated by secretion of proteins from parasite to the host erythrocyte and beyond, collectively known as, malaria secretome.

Structure-based binding between protein farnesyl transferase and PRL-PTP of malaria parasite: an interaction study of prenylation process in Plasmodium.

Protein prenylation is a post-translational modification critical for many cellular processes such as DNA replication, signaling, and trafficking. It is mediated by protein farnesyltransferase by recognizing 'CAAX' motif on protein substrate. Plasmodium falciparum also possesses many such proteins with 'CAAX' motif, involved in various pathways of the parasite.