Synthesis and biological properties of S-adamantylated heterocyclic compounds

A series of new S-adamantylated compounds were prepared by adamanlyl cation attack on the thiol group. The biological activity of new compounds as the inducers of TNF-alpha in genetically modified mouse melanoma cells is presented.     

Synthesis and biological properties of dihydro-oxadiazine-based heterocyclic derivatives

Dihydro-oxadiazine and its derivatives have been demonstrated to be important heterocyclic scaffold platform with bioactive diversity, which present wide activities such as cardiovascular, antitumor, antibacterial, antimicrobial, acricidal, insecticidal, plant-growth regulating, chitin biosynthesis inhibitors and monoamine oxidase inhibition. Versatile features of dihydro-oxadiazine heterocycles have emerged, so the aim of the present paper was to review the recent advances of dihydro-oxadiazine-based heterocyclic derivatives mainly including synthesis and biological activities.     

Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis

Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracyclic dihydropyridopyrazoles. Libraries of these structurally simple analogues are prepared by a straightforward one-step multicomponent synthesis and demonstrated to display antiproliferative properties in a number of human cancer cell lines. These new heterocycles potently induce apoptosis in cancerous Jurkat cells even after a short 24 h exposure. In contrast, no apoptosis is detected in primary lymphocytes under the same treatment conditions. The ease of synthesis and encouraging biological activities make the presented library of dihydropyridopyrazoles promising new leads in anticancer drug design.     

Facile synthesis and biological evaluation of heterocyclic compounds containing diazepam

Diazepamoxadiazoles 4, 5, 6, 12, 14 and 22 were prepared with the binary form system. Diazepamthiadiazoles 15, 20 and Diazepamtriazoles 7, 8, 9, 17, 18, 19 and 21 were also shapely synthesized. Some of these compounds were screened to test their antibacterial activity against E. coli and B. subtilis compounds 15 and 20 show potent activity against these bacteria.     

Synthesis and pharmacological properties of heterocyclic analogs of prostaglandin

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 22, No. 10, pp. 1188–1193, October, 1988.     

Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents

N-Acyl imidates (2), reacting with 5-amino pyrazole (3), 2-aminobenzimidazole (4), 3-amino-1,2,4-triazole (5), 3,5-diamino-1,2,4-triazole (6), and 5-aminotetrazole (7) give pyrazolo[1,5-a][1,3,5]triazine (8), benzo[4,5]imidazo[1,2-a][1,3,5]triazine (9), [1,2,4]triazolo [2,3-a][1,3,5]triazine (10), [1,2,4]tri azolo[2,3-a][1,3,5]triazin-5-ylamine (12), and tetrazolo-[1,5-a][1,3,5]triazine (14) derivatives, respectively. The synthesized compounds were characterized on the basis of IR, (1)H-NMR, (13)C-NMR, and mass spectral data and elemental analyses results. Five of the newly synthesized compounds, 8a, 9a, 10a, 12a, and 14a, were selected by National Cancer Institute and screened for their anticancer activity against three cancer cell lines MCF7, NCI-H460, and SF-268, where 12a exhibited moderate anti-proliferation potential. 12a was, thus, further tested for anticancer activity against 60 human cancer cell lines and showed moderate growth inhibition potency. 12a showed a high growth inhibitory activity against A498 renal cancer cell line. All of the newly synthesized compounds 8-10, 12 and 14 were tested for their antioxidant capacity where they exhibited very high activity, even higher than the widely used reference antioxidants butylated hydroxytoluene and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Compound 12a also showed the highest antioxidant activity.     

Synthesis and biological properties of some novel heterocyclic homoprostanoids.

In the search for prostaglandin-like structures capable of exerting specific and desirable biological properties, a variety of simple heterocyclic homoprostanoidal derivatives was synthesized from readily available stearic acid derivatives. Compounds 5b and 5e were found to be more than 100 times as potent as PGE1 and PGE2 in a tracheal chain bioassay and, like 6, 9, and 12, inhibited PGE2-induced diarrhea. Derivatives 6 and 7a showed significant PG-synthetase inhibitor activity.     

Pharmacological properties of new heterocyclic derivatives of 1,5-benzodiazepine

Sixteen new heterocyclic 1,5-benzodiazepine derivatives (compounds AN8-AN24) were screened for their central action. Compounds AN8-AN10 and AN17 strongly antagonized the action of pentetrazol, compounds AN10, AN14-AN17 and AN22 had potent antiserotonin properties, and compounds AN10, AN19, AN20 and AN23 markedly potentiated the action of DOPA.     

Anticancer properties of an important drug lead podophyllotoxin can be efficiently mimicked by diverse heterocyclic scaffolds accessible via one-step synthesis

Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on β-tubulin, provided a theoretical understanding of these successful experimental findings.     

Activated nitriles in heterocyclic synthesis novel synthesis of thiadiazolo[2,3-a]pyridine derivatives

Several new thiadiazolo[2,3-a]pyridine, thiazole and coumarin derivatives were synthesized via the reaction of 2-cyanomethylthiadiazole with cinnamonitrile, mercaptoacetic acid and salicylaldehyde.