0000000000136277
AUTHOR
Liuqing Yang
Synthesis and structure-activity relationship studies of cytotoxic cinnamic alcohol derivatives.
Three series of di- and trisubstituted derivatives of cinnamic alcohol and its conjugated dienol analogues were designed and synthesised. The derivatives were screened for cytotoxicity against nine tumour cell lines: KB, A549, Hela, CNE, PC-3, BEL-7404, HL-60, BGC823 and P388D1. Most of the cinnamic alcohol derivatives showed cytotoxic activity. The compound 7-(4',5'-dichlorobenzyloxy)-6,8-dihydroxycinnamic alcohol (55) exhibited significant cytotoxicity to seven human tumour cell lines on a micromolar range, especially with regard to the KB and P388D1 cell lines, showing IC(50) values of 0.4 and 0.5 µM, respectively. The structure-activity relationships of the derivatives are discussed.
A facile chemoenzymatic approach: one-step syntheses of monoterpenoid indole alkaloids.
Facile chemoenzymatic syntheses of cytotoxic monoterpenoid indole alkaloids with novel skeletons and multiple chiral centers are described. Synthesis of these alkaloids was achieved by a simple one-step reaction using strictosidine and 12-aza-strictosidine as the key intermediates. Strictosidines were prepared by coupling of secologanin with tryptamine and 7-aza-tryptamine, respectively, using the immobilized recombinant Rauvolfia strictosidine synthase. A detailed stereochemical analysis is presented herein. The results provide an opportunity for a chemoenzymatic approach that leads to an increased diversification of complex alkaloids with improved structures and activities.
Improved Expression of His6-Tagged Strictosidine Synthase cDNA for Chemo-Enzymatic Alkaloid Diversification
Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of stricto…
Strukturbasis und Enzymmechanismus der Biosynthese von C9- aus C10-monoterpenoiden Indol-Alkaloiden
Alle Neune: Die dreidimensionale Struktur der Polyneuridinaldehyd-Esterase (PNAE) gibt einen Einblick in den Enzymmechanismus der Biosynthese von C9- aus C10-monoterpenoiden Indol-Alkaloiden (siehe Schema). PNAE ist eine sehr substratspezifische Serin-Esterase. Sie enthalt die katalytische Triade S87-D216-H244 und ist ein neues Mitglied der Superfamilie der α/β-Hydrolasen, allerdings mit einer neuartigen Funktion: der Diversifizierung von Alkaloidstrukturen.
Structural Basis and Enzymatic Mechanism of the Biosynthesis of C9- from C10-Monoterpenoid Indole Alkaloids
Cutting carbons: The three-dimensional structure of polyneuridine aldehyde esterase (PNAE) gives insight into the enzymatic mechanism of the biosynthesis of C(9)- from C(10)-monoterpenoid indole alkaloids (see scheme). PNAE is a very substrate-specific serine esterase. It harbors the catalytic triad S87-D216-H244, and is a new member of the alpha/beta-fold hydrolase superfamily. Its novel function leads to the diversification of alkaloid structures.