Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines and their Mannich bases.

A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15µM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20µM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.

Synthesis, antitumor, antitrypanosomal and antileishmanial activities of benzo[4,5]canthin-6-ones bearing the N'-(Substituted benzylidene)-carbohydrazide and N-Alkylcarboxamide groups at C-2.

A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC(50) values in the range of 1.15-8.46 µM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC(50) in the range of 0.4 to 16.70 µM.

Synthesis and evaluation of new ß-carboline-3-(4-benzylidene)-4H-oxazol-5-one derivatives as antitumor agents.

In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-ß-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-ß-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50 values of 0.48, 1.50 and 1.07 µM, respectively. An in silico study of the ADME properties of the novel synthesized ß-carboline derivatives was also performed.

Synthesis and antitumor activity of ß-carboline 3-(substituted-carbohydrazide) derivatives.

A series of ß-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The ß-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of ß-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 µM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 µM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.

Methyl 4-{[6-(4-bromo-phen-yl)-3-oxo-2,3,4,5-tetra-hydro-pyridazin-4-yl]methyl}benzoate.

The structure of the title compound, C(19)H(17)BrN(2)O(3), consists of two cyclic groups, viz. 4-(meth-oxy-carbon-yl)phenyl and 6-(4-bromo-phen-yl)-3-oxo-2,3,4,5-dihydro-pyridazin-4-yl, which are linked by a methyl-ene spacer. The pyridazine ring is twisted and the dihedral angle between its mean plane and that of the bromo-phenyl mean plane is 17.2 (2)°. The 4-(meth-oxy-carbon-yl)phenyl group shows a quasi-planar conformation, where the dihedral angle between the mean planes of the phenyl ring and carboxyl-ate ester group is 7.9 (4)°. Centrosymmetric inter-molecular N-H⋯O hydrogen bonds form dimers. These are linked by C-Br⋯O=C inter-actions [Br⋯O = 3.10 (1) Å] to form a one-dimensional polymeric structure running along the [1[Formula: see text]0] direction.