grandisin and tetrahydrofuran

Myristica fragrans Houtt., the source of very important spice 'nutmeg' used world over is native to India, Indonesia, Sri Lanka, South Africa and Southeast Asia. Phytochemical investigation of M. fragrans stem bark led to the isolation of bis-aryl dimethyl tetrahydrofuran lignans, such as grandisin [(7S,8S,7'S,8'S)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan] and (7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan along with important lignans and neolignans, licarinA, licarin B, odoratisol A, (2S, 3R)-7-methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(5-methoxy,3,4-methylenedioxyphenyl)-2,3-dihydrobenzofuran, elemicin, fragransin B

Topics: Anisoles; Benzofurans; Dioxoles; Furans; India; Indonesia; Lignans; Molecular Structure; Myristica; Phytochemicals; Plant Bark; Spectrum Analysis; Sri Lanka

Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

Topics: Animals; Antiprotozoal Agents; Furans; Humans; Leishmania; Leishmaniasis; Lignans; Macrophages; Nitric Oxide; Structure-Activity Relationship

Two new tetrahydrofuran lignans, kadlongirins A and B (1, 2), a new cadinane-type sesquiterpenoid, 2,7-dihydroxy-11,12-dehydrocalamenene (3), together with seven known lignans, grandisin, fragransin B1, vladirol F, kadsuralignan C, otobaphenol, isoanwulignan, and 4-[4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxy-phenol, were isolated from the leaves and stems of Kadsura longipedunculata. The structures of these new compounds were elucidated by spectroscopic methods. Compound 2 exhibited weak anti-human immunodeficiency virus-1 activity with an EC50 value of 16.0 microg/ml, and therapeutic index (TI) value of 6.7.

Topics: Anti-HIV Agents; Drugs, Chinese Herbal; Furans; Humans; Kadsura; Lignans; Microbial Sensitivity Tests; Molecular Structure; Phytotherapy; Sesquiterpenes