Synthesis and analgesic activity of new compounds combining azaadamantane and monoterpene moieties

Ponomarev, Konstantin; Павлова, А. В.; Суслов, Е. В.; Ardashov, Oleg V.; Корчагина, Д. В.; Nefedov, Andrey A.; Толстикова, Т. Г.; Волчо, К. П.; Salakhutdinov, N. F.

doi:10.1007/s00044-015-1464-z

Cited by 28 publications

(20 citation statements)

References 35 publications

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“…Some Myrtenal-based ester derivatives are proven to have great insecticidal activity [27]. In 2015, novel Myrtenal hybrids were successfully tested as potent analgesic [28]. Nonetheless, none report the synthesis pseudo-peptides decorated with Myrtenyl core for the evaluation of the cytotoxic activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

et al. 2020

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Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2–oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

et al. 2020

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“… 16 Here, we screened over 170 natural derivatives in a Marburg glycoprotein-mediated VSIV pseudotype system. The library of natural compounds includes the derivatives of (+)-camphor, 17 , 18 (–)-borneol, 19 , 20 dehydroabietylamine, 21 , 22 para -mentha-1,8-dien-5,6-diol, 23 – 26 (–)-isopulegol, 27 deoxycholic acid, 28 (+)-usninic acid, 29 aminoadamantane 30 , 31 and azaadamantane 32 which were previously described by our colleagues. Among the tested derivatives, the bornyl ester containing saturated N-heterocycles exhibited the highest antiviral activity with several hit compounds identified.…”

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confidence: 99%

N-Heterocyclic borneol derivatives as inhibitors of Marburg virus glycoprotein-mediated VSIV pseudotype entry

et al. 2017

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“…For the synthesis of target substances, nesessary starting compounds were synthesized ( Figure 2). The synthesis of 1,3-diazaadamantane (2) and 1,5-dimethyl-3,7-diazabicyclo [3.3.1]nonan-9-one (3) was carried out according to the procedure [26]. 2-(Bromomethyl)-6,6-dimethylbicyclo [3.1.1]hept-2-ene (4) ( Figure 2) was obtained according to the procedure [27].…”

Section: Synthesis Of Bispidine Derivativesmentioning

confidence: 99%

The effect of 3,7-diazabicyclo[3.3.1]nonanescontaining monoterpenoid moieties on the physical activity of mice.

Kotlyarova¹,

Ponomarev²,

Морозова³

et al. 2020

jrp

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The aim of this work is to study the effect of agents combining fragments of monoterpenoids and 3,7diazabicyclo[3.3.1]nonane (bispidine) on the performance of mice. Physical endurance was studied using two tests: exhaustive swimming with a load of 7% of body weight (after single dosing) and exhaustive treadmill running (after single dosing and a 7-day administration). It has been shown for the first time that derivatives of monoterpenoids with 3,7-diazabicyclo[3.3.1]nonane moiety containing methyl substituents at positions 1 and 5 have a stimulatory effect on the performance of mice, which exceeds the effect of the reference drug bromantane after single dosing. Compound K1-458, which contains (-)-myrtenal residues linked to a bispidine fragment via amino groups, is the most effective in increasing the duration of running and swimming at a dose of 100 mg/kg after single intragastric administration. It has been also established that the LD50 for these compounds exceeds 1,000 mg/kg.

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Synthesis and analgesic activity of new compounds combining azaadamantane and monoterpene moieties

Cited by 28 publications

References 35 publications

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

N-Heterocyclic borneol derivatives as inhibitors of Marburg virus glycoprotein-mediated VSIV pseudotype entry

The effect of 3,7-diazabicyclo[3.3.1]nonanescontaining monoterpenoid moieties on the physical activity of mice.

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