Impact of new cyclooxygenase 2 inhibitors on human cytomegalovirus replication in vitro

Background Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity. Purpose: As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxychalcone compounds to inhibit human cytomegalovirus. Study design We first selected the most efficient new synthetic chalcones for their effect against COX-2-catalyzed PGE2. Study sample Among the selected compounds, we assessed the antiviral efficacy against different HCMV strains, such as the laboratory strain AD169 and clinical strains (naïve or multi-resistant to conventional drugs) and toxicity on human cells. Results The most efficient and less toxic compound (chalcone 7) was tested against HCMV in combination with other antiviral molecules: artesunate (ART), baicalein (BAI), maribavir (MBV), ganciclovir (GCV), and quercetin (QUER) using Compusyn software. Association of chalcone 7 with MBV and BAI is synergistic, antagonistic with QUER, and additive with GCV and ART. Conclusion These results provide a promising search path for potential bitherapies against HCMV.

Some groups of drugs which use is associated with development of drug-induced atrial fibrillation

Recently, more and more attention has been paid to the problem of drug‑induced (DI) atrial fibrillation (AF). It is known that the development of DI AF can be associated with the intake of cardiovascular and anticancer drugs, drugs that affect the central nervous system or respiratory organs. However, there are other drugs that can provoke DI AF, which practitioners are less aware of. This article is a review of the current literature on DI AF associated with the intake of other groups of drugs and individual drugs that are not included in the above groups. Analysis of the available literature has shown that the incidence of DI AF reaches 6.9% when taking zoledronic acid and 1.5% when taking alendronate, although data from different authors regarding the causal relationship between bisphosphonate therapy and the development of AF are ambiguous. The use of high doses of glucocorticosteroids (at a daily dose of ≥ 7.5 mg in terms of prednisolone) is also associated with an increased risk of AF (OR = 6.07; 95% CI: 3.90–9.42). Treatment with non‑steroidal anti‑inflammatory drugs is also associated with a higher risk of developing DI AF compared to those who do not use it – the incidence rate is 1.17 (95% CI: 1.10–1.24) for nonselective and 1.27 (95% CI: 1.20–1.34) for cyclooxygenase‑2 inhibitors. The literature contains a description of clinical cases of DI AF while taking immunosuppressants (azathioprine, methotrexate + etanercept, fingolimod, cyclosporine), drugs that affect the genitourinary system (vardenafil, sildenafil, yohimbine hydrochloride, hexoprenaline), local anesthetics, bupacaero testosterone, stanozolol, testosterone cypionate, nandrolone decanoate extraboline) and nicotine‑containing products (nicotine‑containing chewing gum).

Dual Human Carbonic Anhydrase/Cyclooxygenase-2 Inhibitors: A Promising Approach for Cancer Treatment

: Human carbonic anhydrase (hCA) and cyclooxygenase-2 (COX-2) have been known for a long to be chiefly involved in both the pathogenesis and progression of cancer and cancer chemoresistance. Interestingly, there is emerging evidence that the sulfonamide-type COX-2 selective inhibitors (coxibs) demonstrate inhibitory action against the cancer-related hCA isoforms, confirmed by X-ray crystal structures for celecoxib and valdecoxib complexes with the hCA active site. Consequently, the antineoplastic activity of the sulfonamide coxibs may be justified by the contribution of hCA inhibition to such processes in addition to COX-2 inhibition. Accordingly, these compounds' anti-tumoral activity should be further explored for their possible use in cancer prevention and combination therapy; however, few papers deal with this issue. Beginning with a brief description of the main molecular and catalytic features of both enzymes and their roles in tumor physiology, this review covers a survey of the most recent evidence regarding the molecules targeting one or both of hCA and COX-2, also providing insights into their mechanism of action and efficacy in preventing cancer.