A critique review of fetal hemoglobin modulators through targeting epigenetic regulators for the treatment of sickle cell disease.

Sickle cell disease (SCD) is one of the most prevalent hereditary blood disorders characterized by aberrant hemoglobin synthesis that causes red blood cells (RBCs) to sickle and result in vaso-occlusion. The complex pathophysiological mechanisms that underlie SCD are explored in this study, including hemoglobin polymerization, the formation of fetal hemoglobin (HbF), and hemoglobin switching regulation. Notably, pharmaceutical approaches like hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, in addition to therapeutic techniques like gene therapies like Casgevy and Lyfgenia, signify noteworthy advancements in the management of issues connected to SCD.

Metal-Free, Visible-Light-Mediated Synthesis of Tetracyclic Benzimidazole: Regioselective C-H Functionalization with In Vitro and Computational Study of Anti-breast Cancer Compounds.

Globally, breast cancer is the leading cause of mortality. Within the field of antibreast cancer drug design by several compound docking studies, eight new N-containing nonsteroid tetracyclic derivatives have been synthesized via regioselective intramolecular C-H functionalization by visible light. The adopted methodology is highly efficient, green, and sustainable to unload a new pathway with excellent yield.

In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition.

The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well.

Pharmacoinformatics-based prediction of Checkpoint kinase-1 inhibitors from Momordica charantia Linn. for cancer.

Checkpoint kinase 1 (Chk-1), a serine/threonine kinase family protein, is an emerging target in cancer research owing to its crucial role in cell cycle arrest. Therefore, we aimed to predict potential Chk-1 inhibitors from Momordica charantia Linn., using high-throughput molecular docking.

Identification of Potential Inhibitors from Medicinal Plant-based Phytochemicals for the Influential C4 Target of Diabetic Retinopathy by Molecular Docking Studies.

Introduction: Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the current treatment involves the practice of glucocorticoids or VEGF antagonists that are "off-label". A few small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids, and amino acids that can defer the development of some diseases.

A critical review of therapeutic interventions in sickle cell disease: Progress and challenges.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder that occurs due to the point mutation in the β-globin gene, which results in the formation of sickle hemoglobin (HbS) in the red blood cells (RBCs). When HbS is exposed to an oxygen-depleted environment, it polymerizes, resulting in hemolysis, vaso-occlusion pain, and impaired blood flow. Still, there is no affordable cure for this inherited disease.

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues.

Twenty-eight compounds, , 1,8-naphthyridine-3-carbonitrile (ANC and ANA) derivatives, were designed and synthesized through a molecular hybridization approach. The structures of these compounds were analyzed and confirmed using H NMR, C NMR, LCMS, and elemental analyses. The synthesized compounds were evaluated by testing for their effectiveness against tuberculosis using the MABA assay, targeting the H37Rv strain.

Unlocking nitrogen compounds' promise against malaria: A comprehensive review.

Plasmodium parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment.

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents.

We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, H NMR, C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC values < 16 μM, were the most active compounds.

Design, synthesis and biological evaluation of phenanthridine amide and 1,2,3-triazole analogues against .

The phenanthridine core exhibits antitubercular activity, according to reports from the literature. Several 1,2,3-triazole-based heterocyclic compounds are well-known antitubercular agents. A series of twenty-five phenanthridine amide and 1,2,3-triazole derivatives are synthesized and analyzed using ESI-MS, HNMR, and CNMR on the basis of our earlier findings that phenanthridine and 1,2,3-triazoles shown good antitubercular activity.

Pharmacoinformatics-based identification of phytochemicals from Swartz. fruits as potential inhibitors for MAPK14 protein.

Plants and phytocompounds gained more attention because of their unrivalled variety of chemical diversity. In this view, the present study was executed to predict the anticancer potential of Swartz. fruits derived phytocompounds against one of the breast cancer target proteins (MAPK14, PDB ID: 5ETA, resolution: 2.

Discovery of potent DNMT1 inhibitors against sickle cell disease using structural-based virtual screening, MM-GBSA and molecular dynamics simulation-based approaches.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder affecting millions of people worldwide. A reversible and selective DNMT1 inhibitor, GSK3482364, has been known to decrease the overall methylation activity of DNMT1, resulting in the increase of HbF levels and percentage of HbF-expressing erythrocytes in an and model. In this study, a structure-based virtual screening was done with GSK3685032, a co-crystalized ligand of DNMT1 (PDB ID: 6X9K) with an IC value of 0.

Retrospective Review of Chromane Analogues as Anti-protozoal Leads: A Decade's Worth of Evolution.

Tropical, vector-borne, and neglected diseases with a limited number of medication therapies include Leishmaniasis, Malaria, Chagas and Human African Trypanosomiasis (HAT). Chromones are a large class of heterocyclic compounds with significant applications. This heterocycle has long aroused the interest of scientists and the general public from biosynthetic and synthetic points of view owing to its interesting pharmacological activities.

Filamin A Regulates Cardiovascular Remodeling.

Filamin A (FLNA) is a large actin-binding cytoskeletal protein that is important for cell motility by stabilizing actin networks and integrating them with cell membranes. Interestingly, a -terminal fragment of FLNA can be cleaved off by calpain to stimulate adaptive angiogenesis by transporting multiple transcription factors into the nucleus. Recently, increasing evidence suggests that FLNA participates in the pathogenesis of cardiovascular and respiratory diseases, in which the interaction of FLNA with transcription factors and/or cell signaling molecules dictate the function of vascular cells.

Lack of RAC1 in macrophages protects against atherosclerosis.

The Rho GTPase RAC1 is an important regulator of cytoskeletal dynamics, but the role of macrophage-specific RAC1 has not been explored during atherogenesis. We analyzed RAC1 expression in human carotid atherosclerotic plaques using immunofluorescence and found higher macrophage RAC1 expression in advanced plaques compared with intermediate human atherosclerotic plaques. We then produced mice with Rac1-deficient macrophages by breeding conditional floxed Rac1 mice (Rac1fl/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter (LC).

The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway.

The mut-T homolog-1 (MTH1) inhibitor TH588 has shown promise in preclinical cancer studies but its targeting specificity has been questioned. Alternative mechanisms for the anti-cancer effects of TH588 have been suggested but the question remains unresolved. Here, we performed an unbiased CRISPR screen on human lung cancer cells to identify potential mechanisms behind the cytotoxic effect of TH588.

Targeting Filamin A Reduces Macrophage Activity and Atherosclerosis.

Background: The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.

Methods: We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna ) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC).

Blocking the Cleavage of Filamin A by Calpain Inhibitor Decreases Tumor Cell Growth.

Background/aim: Filamin A (FLNA) is the most abundant and widely expressed isoform of filamin in human tissues. It is cleaved by calpain at the hinge 1 and 2 domains, producing a 90-kDa carboxyl-terminal fragment (FLNA). Recently, it has been shown that FLNA mediates cell signaling and transports transcription factors into the cell nucleus.