The synthesis and biological evaluation of a novel series of dimeric camphor derivatives are described. The resulting compounds were studied for their antiviral activity, cyto- and genotoxicity. Compounds 3a and 3d in which the quaternary nitrogen atoms are separated by the C5H10 and С9H18 aliphatic chain, exhibited the highest efficiency as an agent inhibiting the reproduction of the influenza virus A(H1N1)pdm09. The cytotoxicity data of compounds 3 and 4 revealed their moderate activity against malignant cell lines; compound 3f had the highest activity for the CEM-13 cells. These results show close agreement with the data of independent studies on toxicity of these compounds, in particular that the toxicity of compounds strongly depends on spacer length.
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.
For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were
proposed as potential inhibitors of the SARS-CoV-2 main viral protease
(3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active
site of the protease, a group of compounds were modeled and tested for activity against
3CLpro. The 3CLpro activity was measured using the fluorogenic substrate
Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by
comparison with literature data for ebselen and disulfiram. The results of the
experiments performed with bispidine compounds showed that 14 compounds exhibited
activity in the concentration range 1–10 μM, and 3 samples exhibited
submicromolar activity. The structure–activity relationship studies showed that
the molecules containing a carbonyl group in the ninth position of the bicycle exhibited
the maximum activity. Based on the experimental and theoretical results obtained,
further directions for the development of this topic were proposed.
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