O. I. Yarovaya

Discovery of a new class of antiviral compounds: camphor imine derivatives.

A new class of compounds featuring a camphor moiety has been discovered that exhibits potent inhibitory activity against influenza A(H1N1)pdm09 and A(H5N1) viruses. The synthesized compounds were characterized by spectroscopic analysis; in addition the structures of compound 2 and 14 were elucidated by the X-ray diffraction technique. Structure-activity relationship studies have been conducted to identify the 1,7,7-trimethylbicyclo[2.2.1]heptanes2-ylidene group as the key functional group responsible for the observed antiviral activity. The most potent antiviral compound is imine 2 with therapeutic index more than 500.

Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo

Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm09, H3 and H5 subtypes) and B with EC50s lying in micromolar range. Due to low cytotoxicity it resulted in high selectivity indices (74-661 depending on the virus). This effect did not depend on susceptibility or resistance of the viruses to adamantane derivatives amantadine and rimantadine. The compound appeared the most effective when added at the early stages of viral life cycle (0-2h p.i.). In direct hemagglutinin inhibition tests camphecene was shown to decrease the activity of HAs of influenza viruses A and B. The activity of camphecene was further confirmed in experiments with influenza virus-infected mice, in which, being used orally by therapeutic schedule (once a day, days 1-5 p.i.) it decreased specific mortality of animals infected with both influenza A and B viruses (highest indices of protection 66.7% and 88.9%, respectively). Taken together, these results are encouraging for further development of camphecene-based drug(s) and for exploration of camphor derivatives as highly prospective group of potential antivirals.

Monoterpenes as a renewable source of biologically active compounds

Abstract Monoterpenes and their derivatives play an important role in the creation of new biologically active compounds including drugs. The review focuses on the data on various types of biological activity exhibited by monoterpenes and their derivatives, including analgesic, anti-inflammatory, anticonvulsant, antidepressant, anti-Alzheimer, anti-Parkinsonian, antiviral, and antibacterial (anti-tuberculosis) effects. Searching for novel potential drugs among monoterpene derivatives shows great promise for treating various pathologies. Special attention is paid to the effect of absolute configuration of monoterpenes and monoterpenoids on their activity.

Transformations of 6,7-Epoxy Derivatives of Citral and Citronellal in Various Acidic Media

The transformations of 6,7-epoxy derivatives of widely spread in the nature unsaturated aldehydes, citral and citronellal, in various acidic media both under conditions of homogeneous and heterogeneous catalysis were investigated. A number of previously unknown products belonging to different classes of organic compounds was obtained. Probable mechanisms of the products formation are discussed.

[Curare-Like Camphor Derivatives and Their Biological Activity].

The synthesis of symmetric dimeric camphor derivatives containing two quaternary nitrogen atoms was performed and their myorelaxant activity in mice was evaluated. For the comparison, some salts derived from meta- and para-xylylene dibromides were synthesized and their activity was tested.

Synthesis of Epoxy Dinitriles from Citral and Their Acid- Catalyzed Transformations

Abstract2,3-and 6,7-Epoxy derivatives of citral react with malononitrile in the presence of basic Csβ-zeolite to give the corresponding epoxyalkenylidenemalononitriles as the major products. Epoxy dinitriles obtained from 6,7-epoxycitral undergo acid-catalyzed transformations into tetrahydrofuran derivatives or acyclic polyenes containing hydroxy and cyano groups, depending on the catalyst nature.

Intramolecular Involvement of an Oxygen-containing Nucleophilic Group in Epoxy Ring Opening

The objective of the review is analysis of reactions occurring in epoxy compounds with additional oxygen-containing group (carbonyl, epoxy ring or alcohol group) attached to its skeleton, and the description of the biological aspects of the reactions. The mechanisms of the reactions, the stereo- and regioselectivity of transformations are discussed.

Synthesis and biological activity of heterocyclic borneol derivatives

A series of novel heterocyclic derivatives of (–)-borneol has been prepared by the interaction of (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]-heptan-2-yl 2-chloroacetate and (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-chloropropanoate with different N- and S-nucleophiles. The obtained products were screened for antiviral, antiulcer, and analgesic activity.

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.

Transformations of diepoxy derivatives of limonene in homogeneous acidic media

Transformations of diepoxy derivatives of limonene under conditions of homogeneous acid catalysis were studied, and their results were compared with those obtained over heterogeneous catalysts. A number of previously unknown compounds were isolated. The most possible transformation pathways were analyzed by computer simulation using molecular-mechanics and quantum-chemical methods.