Synthesis and antimicrobial activity of novel 1,2,3-triazole-conjugates of quinazolin-4-ones.

A novel series of diethyl{4-[(4-oxoquinazolin-3(4H)-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates 9aa-aj and their respective derivatives substituted at C6 of the quinazolinone moiety with a bromine atom (9ba-bj) or a nitro group (9ca-cj) were synthesized and assessed for the antibacterial activity toward selected Gram-positive and Gram-negative bacteria. Their antifungal activity was also screened. Compound 9ac was found to be the most active against Staphylococcus aureus ATCC 6535 (MIC 0.625 mg/mL, MBC 1.25 mg/mL), phosphonates 9ab-ai showed promising activity against Enterococcus faecalis ATCC 29212 (MIC = 0.625 mg/mL, MBC = 1.25 mg/mL), while compounds 9ac-j appeared the most active toward Pseudomonas aeruginosa ATCC 27853 (MIC = 0.625 mg/mL, MBC = 1.25 mg/mL). Antifungal assays of compounds 9aa-aj, 9ba-bj, and 9ca-cj were conducted on Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 and revealed noticeable activity of 9aa-aj (MIC = 1.25 mg/mL).

Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates.

A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC50 (50% effective concentration) = 27.6-91.5 µM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK-) VZV strain (EC50 = 27.59 µM), while 16d was the most potent towards TK⁺ VZV (EC50 = 29.91 µM). Cytostatic properties of the compounds 14a-i-17a-i were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC50 (50% inhibitory concentration) = 29-130 µM] and L1210 cells [IC50 (50% inhibitory concentration) = 14-142 µM].

Abuse of fentanyl: An emerging problem to face.

Fentanyl is a potent synthetic opioid used as a narcotic analgesic supplement in general and regional anesthesia as well as in management of persistent, severe chronic pain. Alarming epidemiological and forensic medicine reports, accumulated mainly during the last two decades, point to a growing increase in illicit use of fentanyl, mainly in North America and Europe. Toxicological data indicates that fentanyl use is inextricably linked with polydrug use. There are two main sources of fentanyl on the "recreational" drug market. First, the most common, combines illicitly manufactured fentanyl from clandestine sources. The drug is often mixed up with heroin ("fake heroin") to increase its potency at a little cost, or included in cocaine products. It can also be mixed into and sold as oxycodone-, hydrocodone- or alprazolam-containing tablets. The other way to gain fentanyl is through the diversion of fentanyl-containing medicines, especially transdermal patches (FTPs). Fentanyl extracted from FTP can be administered intravenously, insufflated or inhaled after volatilization. The drug can also be delivered by oral or transmucosal application of the whole patch, or by rectal insertion. The most common overdose symptoms are coma, lethargy, respiratory depression and arrest. Although naloxone, an opioid receptor antagonist, is the standard drug for fentanyl overdose rescue, attempts to revive patients with naloxone could be unsuccessful, due to the rapid onset of fentanyl's action. As the fentanyl problem is constantly growing, there is an urgent need for new, effective harm-reduction strategies and technologies, as well as overdose maintenance.