Antifungal activity of bicyclic monoterpenoids and terpenesulfides

Abstract

A total of 33 compounds including bicyclic monoterpenes, oxides, allyl alcohols, and S-containing pinane and carane derivatives were screened for antifungal activity against mycelial and yeast-like fungi. The structure-activity relationship was studied. The most active antimycotics were found.Keywords: carane and pinane monoterpenoids, antifungal activity.We performed for the first time a systematic study of the antifungal activity of series of pinane and carane monoterpenoids with a broad set of S-containing functional groups and studied the structure-activity relationship to find the most active antimycotics.At the start of our work, the literature contained data on the antifungal activity of D-and E-pinenes in addition to the antifungal effect of essential oils containing (+)-3-carene (1), verbenols, and myrtenol [1][2][3][4][5]. However, the antifungal activity of S-containing terpenoids was not previously investigated.Carane thioterpenoids 4-15 were synthesized by reacting stereoisomeric 3-carene oxides (2 and 3) with thiols (4, 5, 10, 11, 15), isothiuronium salts (6-9, 13, 14), and thiourea (16) in the presence of sodium ethoxide [6-9]. Sulfoxide 12 was obtained by oxidation of 6 with H 2 O 2 in glacial acetic acid. The products were isolated by column chromatography. The structures were established using spectral data.

Enzymatic Chemistry of Cyclopropane, Epoxide, and Aziridine Biosynthesis

“…43,44 Some carene derivatives are known to have strong local anesthetic, anti-inflammatory, and antifungal activities. 62,63 In the initial step of the 3-carene synthase-catalyzed reaction, geranyl pyrophosphate (GPP, 19 ) undergoes a syn -1,3-isomerization to linalyl pyrophosphate (LPP, 47a ). The LPP intermediate can have either R - or S - configuration at C3 depending on the particular monoterpene synthase involved and the GPP binding mode in the enzyme active site.…”

Thiylation of (R)-4-Menthen-3-one and Its Derivatives

“…The results acquired a special significance because it is known [7][8][9] that S-containing derivatives of mono-and bicyclic monoterpenoids exhibit various types of biological activity. We performed a series of experiments on electrophilic (with catalysis by ZnCl 2 or BF 3 OEt 2 ) and nucleophilic (in the presence of K 2 CO 3 or AcONa) addition of thiols [PhSH, n-C 12 H 25 SH, HS(CH 2 ) 2 SH] to (R)-4-menthen-3-one (1) in various solvents at 20 or 55°C.…”

Sulfur-Containing Monoterpenoids as Potential Antithrombotic Drugs: Research in the Molecular Mechanism of Coagulation Activity Using Pinanyl Sulfoxide as an Example

“…We have recently created a series of sulfur-containing terpenoids of varied structures with the large set of the functional groups (Ishmuratov et al, 2014 ). Moreover, we also demonstrated the anti-fungal, anti-inflammatory, anti-helicobacter, antimicrobial and other types of activities of sulfur-containing monoterpenoids (Nikitina et al, 2009 , 2010 , 2012a , b ; Gavrilov et al, 2010 ). Coagulation activity of these compounds has already been described in our previous publications (Kiselev et al, 2017 ; Nikitina et al, 2017a , b ).…”