5-Methoxytryptamine reacts with natural food flavour to produce 6-methoxy tetrahydro-ß-carbolines: in vitro investigation of their antioxidant and cytotoxicity properties.

Various 6-methoxytetrahydro-ß-carboline derivatives, namely BEN (6-methoxy-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ANI (6-methoxy-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ACE (6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole) and VAN (2-methoxy-4-(6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-l)phenol), were prepared via the Maillard reaction using food flavours and 5-methoxytryptamine in aqueous medium and were investigated for their in vitro antioxidant and cytotoxicity properties. These derivatives were found to exhibit moderate antioxidant properties, based on a combination of DPPH, ABTS and FRAP assays. The results suggested that the Maillard reaction could be used to generate ß-carboline antioxidants. It was beneficial that VAN showed the highest antioxidant activity but the least cytotoxic activities on non-tumourous cell lines of NIH/3T3, CCD18-Co and B98-5 using MTT assay. ACE, ANI and BEN showed mild toxicity at effective antioxidative concentrations derived from DPPH and ABTS assays. Furthermore, they are safer compared to 5-fluorouracil, cisplatin and betulinic acid on NIH/3T3, CCD18-Co and B98-5 cells. In conclusion, the antioxidant and cytotoxicity properties of 6-methoxytetrahydro-ß-carbolines were demonstrated for the first time.

Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue.

BACKGROUND: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. MATERIALS AND METHODS: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. RESULTS: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 µM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). CONCLUSIONS: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

Bis(6-meth-oxy-1-methyl-2,3,4,9-tetra-hydro-1H-ß-carbolin-2-ium) tetra-chloridozincate(II) dihydrate.

The asymmetric unit of the title compound, (C(13)H(17)N(2)O)(2)[ZnCl(4)]·2H(2)O, contains two tetra-hydro-harmine cations, one tetra-chloro-zincate(II) anion and two water mol-ecules. In the cations, the two 1H-indole ring systems are essentially planar, with maximum deviations of 0.016 (2) and 0.018 (2) Å, and both tetra-hydro-pyridinium rings show a half-chair conformation. The Zn(II) complex anion has a distorted tetra-hedral geometry. In the crystal, inter-molecular N-H⋯O, N-H⋯Cl, O-H⋯O, O-H⋯Cl and C-H⋯O hydrogen bonds link the components into a three-dimensional network. A π-π inter-action with a centroid-centroid distance of 3.542 (14) Šis also observed.

6-Meth-oxy-1-(4-meth-oxy-phen-yl)-1,2,3,4-tetra-hydro-9H-ß-carbolin-2-ium acetate.

In the title compound, C(19)H(21)N(2)O(2) (+)·C(2)H(3)O(2) (-), the 1H-indole ring system is essentially planar [maximum deviation = 0.0257 (14) Å] and forms a dihedral angle of 87.92 (7) Šwith the benzene ring attached to the tetra-hydro-pyridinium fragment. The tetra-hydro-pyridinium ring adopts a half-chair conformation. In the crystal, cations and anions are linked by inter-ionic N-H⋯O, C-H⋯O and C-H⋯N hydrogen bonds into chains along the a axis.