Cytomegalovirus Mutants Resistant to Ganciclovir and Cidofovir Differ in Susceptibilities to Synguanol and Its 6-Ether and 6-Thioether Derivatives

Abstract

bThe methylenecyclopropane nucleoside (MCPN) analogs synguanol and its 6-alkoxy (MBX2168) and 6-alkylthio (MBX1616) derivatives retained good in vitro activities against several common ganciclovir-resistant UL97 kinase variants of human cytomegalovirus. Foscarnet-MCPN cross-resistance was observed among UL54 polymerase variants. UL54 exonuclease domain ganciclovir-cidofovir dual-resistant variants were remarkably more hypersensitive to these MCPNs than to cyclopropavir, with some 50% effective concentration ratios that were <0.1؋ the wild type. Different categories of MCPNs may have therapeutically exploitable mechanistic differences in viral DNA polymerase inhibition.

Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

“…Medications currently being investigated for treatment of CMV include maribavir, leflunomide, cyclopropavir, synguanol, letermovir (AIC246), and artesunate. 8,[102][103][104][105][106][107][108] In addition, brincidofovir is a lipid conjugate derivative prodrug of cidofovir with broad activity against double-stranded DNA viruses, including CMV, and it has been used in small series to successfully treat refractory or resis-tant CMV infections. 109,110 It has enhanced potency compared with cidofovir and no nephrotoxicity or myelosuppressive effects.…”

Modern Ethiotropic Chemotherapy of Human Cytomegalovirus Infection: Clinical Effectiveness, Molecular Mechanism of Action, Drug Resistance, New Trends and Prospects. Part 2

“…Подобные мутанты формируются в процессе проведения терапии ГЦВ. В pUL54 установлены также мутации, обусловливающие кросс-резистентность к ЦПВ и ФМК (T700A) и мультирезистентность к ГЦВ, ЦДВ, ФМК и ЦПВ (M844V) [42].…”

Novel bisthioether derivatives containing a 1,3,4‐oxadiazole moiety: design, synthesis, antibacterial and nematocidal activities

“…1a,b) that had greater antibacterial activity against tomato and tobacco bacterial wilts, rice bacterial leaf blight and leaf streak, and citrus canker compared with traditional commercial bactericides, such as kocide 3000, thiodiazole copper and bismerthiazol. [7][8][9][10][11][12][13][14][15][16][17] Thioether groups are known to be associated with a broad spectrum of pesticidal bioactivities, for example antiviral, 21,[31][32][33][34][35] antibacterial, [36][37][38][39][40][41] antifungal, 21,39,40 insecticidal 41,42 and nematocidal. 43 Over the past few years, study of the synthesis and pesticidal bioactivity of thioether derivatives has attracted considerable attention and some representative examples of thioether derivatives commercialized as pesticides (e.g.…”