New thiosemicarbazides and 1,2,4-triazolethiones derived from 2-(ethylsulfanyl) benzohydrazide as potent antioxidants.

New thiosemicarbazide derivatives 2-6 were synthesised by reacting 2-(ethylsulfanyl)benzohydrazide with various aryl isothiocyanates. The cyclisation of compounds 2-6 under reflux conditions in a basic medium (aqueous NaOH, 4 N) yielded compounds 7-11 that contain a 1,2,4-triazole ring. All of the synthesised compounds were screened for their antioxidant activities. Compounds 2, 3, and 7 showed better radical scavenging in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, with IC50 values of 1.08, 0.22, and 0.74 µg/mL, respectively, compared to gallic acid (IC50, 1.2 µg/mL). Compound 3 also showed superior results in a ferric reducing antioxidant power (FRAP) assay (3054 µM/100 g) compared to those of ascorbic acid (1207 µM/100 g).

Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues.

Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50=16.68 µM), colon cancer HT-29 (IC50=7.51 µM) and breast cancer MCF-7 (IC50=21.24 µM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

Cyclization vs. cyclization/dimerization in o-amidostilbene radical cation cascade reactions: the amide question.

The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions profoundly modulate the electronics of the stilbene olefinic and NH groups and the corresponding radical cations in ways that influence the efficiency of the cyclization due presumably to conformational and stereoelectronic factors. For example, isobutyramido- stilbene undergoes FeCl(3) promoted cyclization to produce only indoline, while n-butyramidostilbene, under the same conditions, produces both indoline and bisindoline.

Challenges associated with the synthesis of unusual o-carboxamido stilbenes by the Heck protocol: Intriguing substituent effects, their toxicological and chemopreventive implications.

The syntheses of fourteen unusual o-carboxamido stilbenes by the Heck protocol revealed surprising complexity related to intriguing substituent effects with mechanistic implications. The unexpected cytotoxic and chemopreventive properties also seem to be substituent dependent. For example, although stilbene 15d (with a 4-methoxy substituent) showed cytotoxicity on HT29 colon cancer cells with an IC(50) of 4.9 µM, the 3,4-dimethoxy derivative (15c) is inactive. It is interesting to observe that the 3,5-dimethoxy derivative (15e) showed remarkable chemopreventive activity in WRL-68 fetal hepatocytes, surpassing the gold standard, resveratrol. The resveratrol concentration needed to be 5 times higher than that of 15e to produce comparable elevation of NQO1.

N,N'-(Biphenyl-2,2'-di-yl)bis-(furan-2-carboxamide).

The title mol-ecule, C(22)H(16)N(2)O(4), is a 2,2'-disubstituted biphenyl whose phenyl-ene rings are rotated by 66.5 (1)° so as to avoid repulsion by the substituents. Only one of the two amide -NH- fragments engages in hydrogen bonding, and this inter-acts with the amido -C(=O)- acceptor of an inversion-related mol-ecule to generate a hydrogen-bonded dimer.

(E)-N-[2-(Biphenyl-4-ylvin-yl)phen-yl]furan-2-carboxamide.

In the title mol-ecule, C(25)H(19)NO(2), the furyl ring is twisted by 46.3 (1)° with respect to the phenyl-ene ring bearing the amido group. In the stilbene unit, the two phenyl-ene rings (i.e. the rings connected through the -CH=CH- fragment) are twisted by 59.2 (1)°; in the biphenyl-ene unit, the two benzene rings are twisted by 35.5 (1)°. In the crystal structure, mol-ecules are linked by an N-H⋯O(amido) hydrogen bond into a zigzag chain running along the c axis.