Global Cancer Statistics 2022: The Trends Projection Analysis

Cancer is one of the most fatal diseases of recent times that causes several deaths every year. The disease variations in different parts of the world, the impact of available medical facilities, and other socio-economic factors have impacted the proper management of this disease. The comparative statistical data of cancer types like breast, prostate, colon, lung, lymph, blood, brain, and kidney cancers can be used to design treatment strategies and therapeutics development. With the advancement of science, several drugs besides diagnostic methods have emerged to control respective cancer and have assisted in curing this disease to some extent. The comparative statistics analysis for cancer about current prevalence is included here to bring a clear framework for the efforts towards future drug development to manage this disease. The availability of new diagnostics and therapeutics and advanced medical facilities in clinics impact cancer statistics. An evaluation of current trends and statistics of cancer pathology vis-à-vis theranostics (diagnostics as well as therapeutics) progress with possible application in clinical settings constitutes the core part of the discussion in this review

Development of Cytarabine Prodrugs and Delivery Systems for Leukemia Treatment

Importance of the field: Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin’s lymphoma. The drug has a short plasma half-life, low stability, and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been extensively explored to enhance the half-life, stability, and delivery of cytarabine. Among the recent cytarabine prodrugs, amino acid conjugate ValCytarabine and fatty acid derivative CP-4055 (in phase 3 trials) have been investigated for the treatment of leukemia and solid tumors, respectively. Alternatively, delivery systems of cytarabine have emerged for the treatment of different cancers. The liposomal-cytarabine formulation (DepoCyt®) has been approved for the treatment of lymphomatous meningitis. Areas covered in this review: Various prodrug strategies evaluated for cytarabine are discussed. Then, the review summarizes the drug delivery systems that have been used for more effective cancer therapy. What reader will gain: This review provides in-depth discussion of the prodrug strategy and delivery systems of cytarabine derivatives for the treatment of cancer. The design of cytarabine prodrugs and delivery systems provide insights for designing the next generation of more effective anticancer agents with enhanced delivery and stability. Take home message: Strategies on designing cytarabine prodrug and delivery formulations showed great promise in developing effective anticancer agents with better therapeutic profile. Similar studies with other anticancer nucleosides can be an alternative approach to gaining access to more effective anticancer agents

N-Myristoylglutamic Acid Derivative of 3′-Fluoro-3′- Deoxythymidine as an Organogel

Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3′-Fluoro-3′-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent

\u3cem\u3eN\u3c/em\u3e-Myristoylglutamic acid derivative of 3′-fluoro-3′-deoxythymidine as an organogel

Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3′-Fluoro-3′-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent

Nanotherapeutics and HIV: Four Decades of Infection Canvass the Quest for Drug Development Using Nanomedical Technologies

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part of extensive studies for application in real settings for the delivery of NRTIs, NNRTIs, microbicides, and siRNA. The positional standing of research in quest of potential therapeutics for combating HIV infection in reference for four decades with this virus need a rational evaluation of nanotechnology to achieve a practical solution to save the lives

Cleaning the molecular machinery of cells via proteostasis, proteolysis and endocytosis selectively, effectively, and precisely: intracellular self-defense and cellular perturbations

This is an accepted manuscript of an article published by Royal Society of Chemistry in Molecular Omics on 02/11/2020, available online: https://doi.org/10.1039/D0MO00085J The accepted version of the publication may differ from the final published version.Network coordinates of cellular processes (proteostasis, proteolysis, and endocytosis), and molecular chaperones are the key complements in the cell machinery and processes. Specifically, cellular pathways are responsible for the conformational maintenance, cellular concentration, interactions, protein synthesis, disposal of misfolded proteins, localization, folding, and degradation. The failure of cellular processes and pathways disturbs structural proteins and the nucleation of amyloids. These mishaps further initiate amyloid polymorphism, transmissibility, co-aggregation of pathogenic proteins in tissues and cells, prion strains, and mechanisms and pathways for toxicity. Consequently, these conditions favor and lead to the formation of elongated amyloid fibrils consisting of many-stranded β-sheets (N,N-terminus and C,C-terminus), and abnormal fibrous, extracellular, proteinaceous deposits. Finally, these β-sheets deposit, and cells fail to degrade them effectively. The essential torsion angles (φ, ψ, and ω) define the conformation of proteins and their architecture. Cells initiate several transformations and pathways during the regulation of protein homeostasis based on the requirements for the functioning of the cell, which are governed by ATP-dependent proteases. In this process, the kinetics of the molding/folding phenomenon is disturbed, and subsequently, it is dominated by cross-domain misfolding intermediates; however, simultaneously, it is opposed by small stretching forces, which naturally exist in the cell. The ubiquitin/proteasome system deals with damaged proteins, which are not refolded by the chaperone-type machinery. Ubiquitin-protein ligases (E3-Ub) participate in all the cellular activity initiated and governed by molecular chaperones to stabilize the cellular proteome and participate in the degradation phenomenon implemented for damaged proteins. Optical tweezers, a single-resolution based technique, disclose the folding pathway of linear chain proteins, which is how they convert themselves into a three-dimensional architecture. Further, DNA-protein conjugation analysis is performed to obtain folding energies as single-molecule kinetic and thermodynamic data.Published versio

Review insights of nanotheranostics for molecular mechanisms underlying psychiatric disorders and commensurate nanotherapeutics for neuropsychiatry: the mind-knockout

© 2021 The Authors. Published by Ivyspring International Publisher. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://dx.doi.org/10.7150%2Fntno.49619Bio-neuronal led psychiatric abnormalities transpired by the loss of neuronal structure and function (neurodegeneration), pro-inflammatory cytokines, microglial dysfunction, altered neurotransmission, toxicants, serotonin deficiency, kynurenine pathway, and excessively produced neurotoxic substances. These uncontrolled happenings in the etiology of psychiatric disorders initiate further changes in neurotransmitter metabolism, pathologic microglial, cell activation, and impaired neuroplasticity. Inflammatory cytokines, the outcome of dysfunctional mitochondria, dysregulation of the immune system, and under stress functions of the brain are leading biochemical factors for depression and anxiety. Nanoscale drug delivery platforms, inexpensive diagnostics using nanomaterials, nano-scale imaging technologies, and ligandconjugated nanocrystals used for elucidating the molecular mechanisms and foremost cellular communications liable for such disorders are highly capable features to study for efficient diagnosis and therapy of the mental illness. These theranostic tools made up of multifunctional nanomaterials have the potential for effective and accurate diagnosis, imaging of psychiatric disorders, and are at the forefront of leading technologies in nanotheranostics openings field as they can collectively and efficiently target the stimulated territories of the cerebellum (cells and tissues) through molecular-scale interactions with higher bioavailability, and bio-accessibility. Specifically, the nanoplatforms based neurological changes are playing a significant role in the diagnosis of psychiatric disorders and portraying the routes of functional restoration of mental disorders by newer imaging tools at nano-level in all directions. Because of these nanotherapeutic platforms, the molecules of nanomedicine can penetrate the Blood-Brain Barrier with an increased half-life of drug molecules. The discoveries in nanotheranostics and nanotherapeutics inbuilt unique multi-functionalities are providing the best multiplicities of novel nanotherapeutic potentialities with no toxicity concerns at the level of nano rangeThe authors thank the National Institute of Medical Sciences, India, for financial support

Copper Triflate-Mediated Synthesis of 1,3,5-triarylpyrazoles in [bmim][PF6] Ionic Liquid and Evaluation of Their Anticancer Activities

A simple, efficient, and environment friendly protocol for the synthesis of 1,3,5-triarylpyrazoles and 1,3,5-triarylpyrazolines in [bmim][PF6] ionic liquid mediated by Cu(OTf)2 is described. The reaction protocol gave 1,3,5-triarylpyrazoles in good to high yields (71–84%) via a one-pot addition–cyclocondensation between chalcones and arylhydrazines, and oxidative aromatization without the requirement for an additional oxidizing reagent. The catalyst can be reused for up to four cycles without much loss in the catalytic activity. The pyrazoles (4a–o) and pyrazolines (3a–n) were evaluated for their antiproliferative activity in SK-OV-3, HT-29, and HeLa human cancer cells lines. Among all the compounds, 3b inhibited cell proliferation of HeLa cells by 80% at a concentration of 50 μM

A Greener Synthesis of 2-Aminochromenes in Ionic Liquid and Evaluation of Their Antiproliferative Activities

An improved simple and facile synthesis of chromene derivatives by employing threecomponent one-pot condensation reaction of β-naphthol, aromatic aldehydes, and malononitrile in ionic liquids is described

Copper(II) triflate-mediated synthesis of 1,3,5-triarylpyrazoles in [bmim][PF6] ionic liquid and evaluation of their anticancer activities

A simple, efficient, and environmentally friendly protocol for the synthesis of 1,3,5-triarylpyrazole in [bimm][PF6] ionic liquid mediated by Cu(OTf)2 is described. The reaction protocol gave 1,3,5-triarylpyrazoles in good to high yields (71-82%) via a one-pot addition–cyclocondensation between hydrazines and chalcones, and oxidative aromatization without requirement for an additional oxidizing reagent. The catalyst can be reused up to four cycles without much loss in the catalytic activity. The pyrazoles (4a-o) and pyrazolines (3a-n) were evaluated for antiproliferative activity in SK-OV-3, HT-29, and HeLa human cancer cells lines. Among all compounds, 3b inhibited cell proliferation of HeLa cells by 80% at a concentration of 50 μM