Identification of sulphonamide-tethered N-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease.

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel triazolo-isatins for inhibiting main protease (Mpro) of the virus, a crucial enzyme for its replication in the host cells. Particularly, sulphonamide 6b showed promising inhibitory activity with an IC50= 0.249 µM. Additionally, 6b inhibited viral cell proliferation with an IC50 of 4.33 µg/ml, and was non-toxic to VERO-E6 cells (CC50 = 564.74 µg/ml) displaying a selectivity index of 130.4. In silico analysis of 6b disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained in vitro findings.

Triterpenoids from the aerial parts of Anabasis articulata (Forssk) Moq: gastroprotective effect in vivo with in silico studies, cytotoxic and antimicrobial activities.

A new triterpenoid named 3ß,20α-dihydroxy-30-nor-olean-12-ene-23,28 dioic acid (4) along with 3ß-hydroxy-23-aldehyde-lup-20(29)-ene-28-oic acid (1), 3ß-hydroxy-23-aldehyde-30-nor-olean-12,20(29)-diene-28-oic acid (2), 3ß-hydroxy-lup-20(29)-ene-23,28 dioic acid (3), 3ß-hydroxy-lup-20(29)-ene-23,28 dioic acid-23-O-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucuronopyranosyl-lup-20(29)-ene-23,28 dioic acid-28-O-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucuronopyranosyl-lup-20(29)-ene-23-aldehyde-28-oic acid-28-O-ß-D glucopyranosyl ester (7) were isolated for the first time from the aerial parts of Anabasis articulata (Forssk) Moq. Isolated pure compounds were structurally elucidated using spectral analysis. Cytotoxic, antimicrobial, antiulcer activities and antioxidant parameters were evaluated using the total methanol extract and its successive fractions. The methylene chloride fraction showed strong cytotoxic activity against HepG-2 (6.9 µg/ml) and HCT-116 (5.5 µg/ml) tumour cell lines in comparative with 5-fluorouracil (7.9 µg/ml). Treatment of indomethacin induced ulcerated rats with ethyl acetate fraction (400 mg/kg, p.o./day) achieved reduced Ulcer index (0.18), potent inhibition percentage of ulceration (84.86%) in comparison to ranitidine and high antioxidant effect. Compound(6) exhibited high docking score against gastric H+/K+ ATPase.

Superior hypogastric block: transdiscal versus classic posterior approach in pelvic cancer pain.

OBJECTIVE: The classic posterior approach of superior hypogastric block has several technical difficulties. The transdiscal approach is a novel and easier approach for superior hypogastric which overcome these technical difficulties. METHODS: Thirty patients were randomly allocated to two groups: The transdiscal group and the classic group; visual analog scale pain scores, daily morphine consumption, duration of the procedure and side effects were recorded. RESULTS: The duration of the procedure was significantly decreased in the transdiscal group (24.4+/-5.6 min) compared to the classic group (57.9+/-9.8 min). There were no significant differences between the 2 groups in daily morphine consumption and VAS pain scores. There was no discitis, disc rupture, or herniation in the transdiscal group. CONCLUSION: The transdiscal approach for superior hypogastric plexus block in pelvic cancer pain is easier, safer, and more effective with less side effects than the classic approach.