Recent synthetic strategies of medicinally important imidazothiadiazoles

Imidazothiadiazole is a fundamental fused heterocyclic compound containing imidazole and thiadiazole ring systems. This versatile framework has significant applications in pharmaceutical chemistry and also possessed a remarkable biological profile. The derivatives of imidazo[2,1-b][1,3,4]thiadiazole have a broad spectrum of biological applications such as antitumor, tubulin inhibitor, anticancer, antifungal, anti-inflammatory, antimicrobial, antitubercular, anticonvulsant, antibacterial and as enzyme inhibitors. These derivatives also play a significant role in the development of non-linear optics and photo-electronics. Synthesis of this fused bicyclic compound mainly involved the reaction between 2-amino-1,3,4-thiadiazoles and α-haloketones, with different substitutions at the 2, 5, and 6 positions of the ring system. Moreover, microwave assisted multicomponent and C–C coupling reactions in the presence of catalysts or under solvent free reaction conditions were found to be reliable and valuable approaches. This review is a concerted approach to describe the synthesis and applications of imidazo[2,1-b][1,3,4] thiadiazole derivatives reported during 2015–2022

Fabrication of hesperidin hybrid lecithin-folic acid silver nanoparticles and its evaluation as anti-arthritis formulation in autoimmune arthritic rat model.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction and loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to adverse effects and patient non-compliance. Hesperidin (HP) is a naturally occurring bioflavonoid having anti-inflammatory and antioxidant properties. In this study, Hesperidin loaded hybrid lecithin-folic acid silver nanoparticles (L-HP-FA-AgNPs) formulation has been developed to deliver HP to inflamed jointsspecifically.Thein vivo anti-inflammatory and anti-arthritic effectsof the formulation were validated in the CFA arthritis rat model by giving oral treatment of L-HP-FA-AgNPs (1 and 3mg/kg) which alleviated the joint swelling, cartilage destruction and reduced influx of inflammatory cells. The results showed decreased pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in the peritoneal and spleen cells coupled with an increase in anti-inflammatory cytokine TGF-β1. Additionally, the treatment caused the decline in M1 macrophage activation with a concomitant increment in M2 macrophage activation. Further, hybrid L-HP-FA-AgNPs suppressed the production of RANKL, OPG and MMP-2/9, which supported its anti-osteoclastic effects. Collectively, our data revealed that L-HP-FA-AgNPs significantly inhibited the progression of arthritis by reducing inflammationand bone damage. The protective effects of hybrid L-HP-FA-AgNPs highlight its potential as an ideal new anti-arthritic agent for human RA.Authors are grateful to the technical team of Dow Institute of Radiology andAdvanceResearch Laboratory, Dow Institute for Advanced Biological and Animal Research, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of Health Sciences, Karachi, Pakistan for the technical assistance during X-ray and animal studies.Scopu

Zinc Oxide Nanoconjugates against Brain-Eating Amoebae

Naegleria fowleri and Balamuthia mandrillaris are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) with mortality rates higher than 90%. Threatening a rise in cases is the increase in temperature due to global warming. No effective treatment is currently available. Herein, nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce N. fowleri viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and B. mandrillaris viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced N. fowleri-mediated and B. mandrillaris-mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for N. fowleri and B. mandrillaris. The MIC50 for N. fowleri were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC50 of the compounds for B. mandrillaris were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections

A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms

Self-reported health and smoking status, and body mass index: a case-control comparison based on GEN SCRIP (GENetics of SChizophRenia In Pakistan) data

Introduction Individuals with schizophrenia are at a high risk of physical health comorbidities and premature mortality. Cardiovascular and metabolic causes are an important contributor. There are gaps in monitoring, documenting and managing these physical health comorbidities. Because of their condition, patients themselves may not be aware of these comorbidities and may not be able to follow a lifestyle that prevents and manages the complications. In many low-income and middle-income countries including Pakistan, the bulk of the burden of care for those struggling with schizophrenia falls on the families.Objectives To determine the rate of self-reported physical health disorders and risk factors, like body mass index (BMI) and smoking, associated with cardiovascular and metabolic disorders in cases of schizophrenia compared with a group of mentally healthy controls.Design A case-controlled, cross-sectional multicentre study of patients with schizophrenia in Pakistan.Settings Multiple data collection sites across the country for patients, that is, public and private psychiatric OPDs (out patient departments), specialised psychiatric care facilities, and psychiatric wards of teaching and district level hospitals. Healthy controls were enrolled from the community.Participants We report a total of 6838 participants’ data with (N 3411 (49.9%)) cases of schizophrenia compared with a group of healthy controls (N 3427 (50.1%)).Results BMI (OR 0.98 (CI 0.97 to 0.99), p=0.0025), and the rate of smoking is higher in patients with schizophrenia than in controls. Problems with vision (OR 0.13 (0.08 to 0.2), joint pain (OR 0.18 (0.07 to 0.44)) and high cholesterol (OR 0.13 (0.05 to 0.35)) have higher reported prevalence in controls. The cases describe more physical health disorders in the category ‘other’ (OR 4.65 (3.01 to 7.18)). This captures residual disorders not listed in the questionnaire.Conclusions Participants with schizophrenia in comparison with controls report more disorders. The access in the ‘other’ category may be a reflection of undiagnosed disorders