TY - JOUR

T1 - Synthesis and analgesic activity of monoterpenoid aldehyde-derived hydro-2H-chromeneols

AU - Il'ina, Irina

AU - Morozova, Ekaterina

AU - Korсhagina, Dina

AU - Volсho, Konstantin

AU - Tolstikova, Tat'yana

AU - Salakhutdinov, Nariman

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Despite a variety of drugs used to stop acute pain, problems related to their insufficient efficacy and undesirable side effects have remained unresolved. Therefore, the search for analgesics of new structural types, which combine high activity with low toxicity, is a topical issue. It is known that a number of compounds with a hydrogenated 2H-chromene skeleton exhibit significant analgesic activity in in vivo tests. Methods: New hydro-2H-chromenols containing monoterpenoid moieties were obtained via one-pot synthesis by the interaction between para-menthane alcohols and commercially available monoterpene aldehydes: Citral, hydroxycitronellal, myrtenal, and perillaldehyde. The analgesic activity of these compounds wаs studied in the acetic acid-induced writhing test and hot plate test. Results: The target compounds were characterized using NMR and HR-MS. Most of them exhibited pronounced analgesic activity. Conclusion: Due to high analgesic activity, (2S,4aR,8R,8aR)-2-((E)-2,6-dimethylhepta-1,5-dien-1-yl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diol is considered as candidate compound to participate in further research.

AB - Background: Despite a variety of drugs used to stop acute pain, problems related to their insufficient efficacy and undesirable side effects have remained unresolved. Therefore, the search for analgesics of new structural types, which combine high activity with low toxicity, is a topical issue. It is known that a number of compounds with a hydrogenated 2H-chromene skeleton exhibit significant analgesic activity in in vivo tests. Methods: New hydro-2H-chromenols containing monoterpenoid moieties were obtained via one-pot synthesis by the interaction between para-menthane alcohols and commercially available monoterpene aldehydes: Citral, hydroxycitronellal, myrtenal, and perillaldehyde. The analgesic activity of these compounds wаs studied in the acetic acid-induced writhing test and hot plate test. Results: The target compounds were characterized using NMR and HR-MS. Most of them exhibited pronounced analgesic activity. Conclusion: Due to high analgesic activity, (2S,4aR,8R,8aR)-2-((E)-2,6-dimethylhepta-1,5-dien-1-yl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diol is considered as candidate compound to participate in further research.

KW - Acetic acid-induced writhing test

KW - Analgesia

KW - Chromene

KW - Hot-plate test

KW - Isopulegol

KW - Monoterpenoid aldehyde

KW - isopulegol

KW - chromene

KW - analgesia

KW - ESTERS

KW - acetic acid-induced writhing test

KW - hot-plate test

UR - http://www.scopus.com/inward/record.url?scp=85078714444&partnerID=8YFLogxK

U2 - 10.2174/1570180816666181114131220

DO - 10.2174/1570180816666181114131220

M3 - Article

AN - SCOPUS:85078714444

VL - 17

SP - 68

EP - 78

JO - Letters in Drug Design and Discovery

JF - Letters in Drug Design and Discovery

SN - 1570-1808

IS - 1

ER -