Molecular Insights into the In Vivo Analgesic and Anti-Inflammatory Activity of Indomethacin Analogues.

The primary objective of this research was to identify and explore the most potent and efficacious cyclooxygenase inhibitors, utilizing indole acetic acid drugs as a lead molecule. To achieve this objective, various derivatives (2a-2c and 2e-2g) of the selected lead molecule, indomethacin, were synthesized using a reflux condensation process, targeting the hydroxyl group. The synthesized analogues were subjected to different spectroscopic procedures to determine their structure and confirm their analogues. These derivatives were further screened for acute toxicity and anti-nociceptive and anti-inflammatory activity using established protocols. Docking analysis was performed to evaluate the possible protein-ligand interaction. The test compounds were found to be safe at doses of 50, 75, 100, and 200 mg/kg, i.p. The pharmacological screening revealed that test compounds 2a-2f had a superior peripheral analgesic effect at a dose of 10 mg/kg, in comparison to the parent drug indomethacin, while compound 2g exhibited slightly lower activity at the same dose. The hot plate results showed lower central analgesic activity of the test compounds compared to the standard Tramal, but it was still significant. Anti-inflammatory results were significant, comparable to Diclofenac sodium and indomethacin, except for compounds 2b, 2c, and 2e at a dose of 10 mg/kg body weight. Molecular docking analysis demonstrated that the derived compounds had augmented negative binding energies (-149.39, -146.72, -160.85, -159.34, -140.03, and -150.91 KJ/mol) compared to the parent drugs (-141.07), which supported the research's theme of producing stronger derivatives of standard drugs with significant anti-nociceptive and anti-inflammatory potential. The derived compounds exhibited significant analgesic and anti-inflammatory activities and, therefore, have the potential to be studied further as new drug candidates for pain and inflammation.

Glyco-nanoparticles: New drug delivery systems in cancer therapy.

Cancer is known as one of the most common diseases that are associated with high mobility and mortality in the world. Despite several efforts, current cancer treatment modalities often are highly toxic and lack efficacy and specificity. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems which are highly selective for tumors and allow a slow release of active anticancer agents. Different Nanoparticles (NPs) such as the silicon-based nano-materials, polymers, liposomes and metal NPs have been designed to deliver anti-cancer drugs to tumor sites. Among different drug delivery systems, carbohydrate-functionalized nanomaterials, specially based on their multi-valent binding capacities and desirable bio-compatibility, have attracted considerable attention as an excellent candidate for controlled release of therapeutic agents. In addition, these carbohydrate functionalized nano-carriers are more compatible with construction of the intracellular delivery platforms like the carbohydrate-modified metal NPs, quantum dots, and magnetic nano-materials. In this review, we discuss recent research in the field of multifunctional glycol-nanoparticles (GNPs) intended for cancer drug delivery applications.

Evaluation of In-vitro Antimicrobial Potential of Daphne retusa Hemsl. Against Human Pathogenic Bacteria and Fungi.

BACKGROUND: Antimicrobial drug resistance is an emerging problem, which leads to a failure in the control of infectious diseases thereby, adversely affecting patient care and reducing effective management of infectious diseases globally. Thus, search for new and more effective alternatives is needed. Daphne retusa Hemsl. (Daphne) has medicinal values and is reported to be widely used in curing a variety of human ailments. OBJECTIVE: Current study assesses in-vitro antimicrobial activity of the crude extract of D.retusa (whole plant) and its derived fractions against clinically isolated human pathogenic bacteria and fungi. MATERIALS AND METHODS: Whole plant of D.retusa was powder dried and then extracted with methanol (E1). The resultant was fractionated to give Chloroform fraction (E2), Butanol fraction (E3) and Ethyl acetate fraction (E4). The crude extract and derived fractions were assessed for antimicrobial and antifungal activity by using agar well diffusion method and their MICs were found following Clinical and Laboratory Standard Institute (CLSI) guidelines. RESULT: Our study shows that D.retusa has very good inhibitory action against different bacterial and fungal strains. All of the extracts were active against almost every microorganism used in the study. E2 has the maximum percent of inhibition against bacterial growth while E1 has themaximum percent of inhibition against fungal growth. Streptococcus pneumonia was the most susceptible bacteria while among fungi, Gongronella butleri showed highest susceptibility. CONCLUSION: Results justify the use of D. retusa in the treatment of microbial infections. For the development of a novel antibiotic, the crude extract and its derived fractions need further exploration; with emphasis to isolate and identify the active constituents that are responsible for antibacterial and antifungal activity.