Essential oils of Uvaria boniana - chemical composition, in vitro bioactivity, docking, and in silico ADMET profiling of selective major compounds.

Phytochemical investigation applying GC (gas chromatography)-MS (mass spectrometry)/GC-FID (flame ionization detection) on the hydro-distilled essential oils of the Vietnamese medicinal plant Uvaria boniana leaf and twig lead to the detection of 35 constituents (97.36%) in the leaf oil and 52 constituents (98.75%) in the twig oil. Monoterpenes, monoterpenoids, sesquiterpenes, and sesquiterpenoids were characteristic of U. boniana essential oils. The leaf oil was represented by major components (E)-caryophyllene (16.90%), bicyclogermacrene (15.95%), α-humulene (14.96%), and linalool (12.40%), whereas four compounds α-cadinol (16.16%), epi-α-muurolol (10.19%), α-pinene (11.01%), and ß-pinene (8.08%) were the main ones in the twig oil. As compared with the leaf oil, the twig oil was better in antimicrobial activity. With the same MIC value of 40 mg/mL, the twig oil successfully controlled the growth of Gram (+) bacterium Bacillus subtilis, Gram (-) bacterium Escherichia coli, fungus Aspergillus niger, and yeast Saccharomyces cerevisiae. In addition, both two oil samples have induced antiinflammatory activity with the IC50 values of 223.7-240.6 mg/mL in NO productive inhibition when BV2 cells had been stimulated by LPS. Docking simulations of four major compounds of U. boniana twig oil on eight relevant antibacterial targets revealed that epi-α-muurolol and α-cadinol are moderate inhibitors of E. coli DNA gyrase subunit B, penicillin binding protein 2X and penicillin binding protein 3 of Pseudomonas aeruginosa with similar free binding energies of -30.1, -29.3, and -29.3 kJ/mol, respectively. Furthermore, in silico ADMET studies indicated that all four docked compounds have acceptable oral absorption, low metabolism, and appropriated toxicological profile to be considered further as drug candidates.

Synthesis of bicuculin by direct condensation method meconin with isoquinolinium iodid salt

Using direct condensation method meconin with isoquinolinium isodid salt, the authors had synthesized of bicuculin by a new method. With this method, an important intermediacy - erythro cordrastin isomer - was created with the greater rate in comparison with threo isomer. Two isomers were separated easily due to silicagel chromatography. The erythro isomer was demethylated by BBr3 reagent. Methylenation of tetrahydroxy compound provided bicuculline racemic. Separate the contrasts of bicucullin racemic by acid D (+) could help to obtain (+) bicucullin with high optical purify which were reached standards for next biological tests

Synthesis of bicucullin by method of forming cycle with Bischler-Napieralski

Phthalideisoquinoline alcaloid norbicuculline have been synthesized by Bischler-Napieralski cyclization. The racemic norbicuculline were resolved into (+) and (-) forms. Methylation of (+ )norbicuculline provided (+)bicuculline. Researching bicucullin synthesis by the method of Bischler – napieralski shows that bicucullin is synthesized from Piperonal and Beta - (3,4 methylendioxy) – phenylethylamin by method of Bischler – napieralski. Isomers of ( ±) erythro and (±) threo norbicucullin are easily separated thank to nhờ sắc kí cột silicagel. Afterwards, optical isomers of (±) norbicucullin are also separated with high optical purity and good output. Methyl changed into (+) erythro norbicucullin is to gather (+) bicucullin gaining standards for biological experiments