Improving the Enantioselectivity of CHMO for Asymmetric Synthesis of Podophyllotoxin Precursor.

(R)-β-piperonyl-γ-butyrolactones are key building blocks for the synthesis of podophyllotoxin, which have demonstrated remarkable potential in cancer treatment. Baeyer-Villiger monooxygenases (BVMOs)-mediated asymmetric oxidation is a green approach to produce chiral lactones. While several BVMOs were able to oxidize the corresponding cyclobutanone, most BVMOs gave the (S) enantiomer while Cyclohexanone monooxygenase (CHMO) from Brevibacterium sp.

Novel shikonin derivatives targeting tubulin as anticancer agents.

In this study, we report the identification of a new shikonin-phenoxyacetic acid derivative, as an inhibitor of tubulin. A series of compounds were prepared; among them, compound 16 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(4- phenoxyphenyl) acetate] potently inhibited the function of microtubules, inducing cell growth inhibition, apoptosis of cancer cell lines in a concentration and time-dependent manner. Molecular docking involving 16 at the vinblastine binding site of tubulin indicated that a phenoxy moiety interacted with tubulin via hydrogen bonding with asparaginate (Asn) and tyrosine (Tyr).

Synthesis and biological evaluation of heterocyclic carboxylic acyl shikonin derivatives.

A series of shikonin derivatives (1-13) that were acylated selectively by various thiophene or indol carboxylic acids at the side chain of shikonin were synthesized, and their biological activities were also evaluated as potential tubulin inhibitors. Among them, compound 3 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 3-(1H-indol-3-yl)propanoate) and compound 8 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(thiophen-3-yl)acetate) exhibited good antiproliferative activity of A875 (IC50  = 0.005 ± 0.

Molecular dynamics simulation of liquid carbon tetrachloride using ab initio force field.

Intermolecular interaction potentials of the carbon tetrachloride dimer in 12 orientations have been calculated using the Hartree-Fock self-consistent theory and the second-order Moller-Plesset (MP2) perturbation theory. We have employed basis sets from Pople's medium size basis sets [up to 6-311++G(3df,3pd)] to Dunning's correlation consistent basis sets (up to aug-cc-pVQZ). The calculated MP2 potential data were employed to parametrize a four-site force field for molecular simulations.