COMPUTER-ASSISTED DRUG DESIGNING OF TRIAZOLE DERIVATIVE OF NOSCAPINE AS TUBULIN-BINDING ANTICANCER DRUG

Objective: Microtubule-interfering drugs are commonly used to treat malignant disorders owing to indispensable role of this cytoskeletal element. These drugs include paclitaxel, docetaxel, and the Vinca alkaloids; however, owing to their non-selective action and overpolymerizing effects, these chemotherapy drugs are confounded by complications with serious toxicity (particularly, peripheral neuropathies, gastrointestinal toxicity, myelosuppression, and immunosuppression) (by taxanes) or depolymerizing effects (by Vincas) on microtubules. Thus, there is urgent need to explore novel tubulin-binding agents that are significantly effective and comparatively less toxic compared to currently available drugs for the treatment of human cancer. The current study focuses fusion of two novel anticancer compounds with low toxicity, i.e., noscapine and triazole to generate a new ligand derivative.Methods: Using computer-aided drug designing approach and molecular docking, molecular interaction of these derivatives with αβ-tubulin heterodimer was confirmed and investigated by molecular docking along with dynamics simulation.Results: A greater affinity of the newly designed ligands for binding to tubulin was predicted. The predictive binding free energy (Gbind,pred) of these derivatives (ranging from −10.5178 to −16.8473 kcal/mol) based on linear interaction energy method with a surface generalized born continuum salvation model showed improved binding affinity with tubulin as compared to the lead compound. natural α-Noscapine (−5.505 kcal/mol). The binding energy of ligand determined using LigX, i.e., MM/GBVI was found to be −23.208 kcal/mol.Conclusion: We found that designed derivative compounds have better efficacy as compared noscapine and triazole

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers

Insights into the emergence and evolution of monkeypox virus: Historical perspectives, epidemiology, genetic diversity, transmission, and preventative measures

In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in humans and resembles smallpox. Prevention strategies encompass vaccination, strict infection control measures, and avoiding contact with infected persons. As monkeypox and related poxviruses continue to pose challenges, ongoing surveillance, early diagnosis, prompt isolation, and effective control measures are crucial for limiting transmission and mitigating the impact of outbreaks on public health. This review provides valuable insights into the evolution of the monkeypox virus and its various modes of transmission, including postmortem transmission, and offers an overall perspective on the guidelines issued by the Government of India to prevent and effectively control the spread of this disease