benzofurans and benzotriazole

A series of novel 3-(1-benzotriazole)-nor-β-lapachones 5a-5l were synthesized as the NQO1-targeted anticancer agents. Most of these compounds displayed good antiproliferative activity against the breast cancer MCF-7, lung cancer A549 and hepatocellular carcinoma HepG2 cells in agreements with their NQO1 activity. Among them, compound 5k was identified as a favorable NQO1 substrate. It could activate the ROS production in a NQO1-dependent manner, arrest tumor cell cycle at G0/G1 phase, promote tumor cell apoptosis, and decrease the mitochondrial membrane potential. In HepG2 xenograft models, 5k significantly suppressed the tumor growth with no influences on animal body weights. Therefore, 5k could be a good lead for further anticancer drug developments.

Topics: Animals; Antineoplastic Agents; Apoptosis; Benzofurans; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Liver Neoplasms, Experimental; Mice; Mice, Nude; Models, Molecular; Molecular Structure; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Structure-Activity Relationship; Triazoles; Tumor Cells, Cultured

Treatment of 2-bromoacetylbenzofuran with 1H-benzotriazole afforded 1-(benzofuran-2-yl)-2-(benzotriazol-1-yl)ethanone which reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivatives. Treatment of the latter ethanone and thioacetanilide derivatives with hydrazonoyl chlorides afforded the corresponding pyrazole and 1,3,4-thiadiazole derivatives. The thioacetanilide derivative reacted with alpha-haloketones and alpha-halodiketones to afford thiophene and thiazole derivatives, respectively. The newly synthesized compounds were found to possess anticonvulsant and anti-inflammatory activities with the same mechanism of action of selective COX-2 inhibitors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Benzofurans; Cyclooxygenase 2 Inhibitors; Drug Evaluation, Preclinical; Heterocyclic Compounds; Mice; Molecular Structure; Stereoisomerism; Structure-Activity Relationship; Triazoles

The stability and replication of DNA containing self-pairs formed between unnatural nucleotides bearing benzofuran, benzothiophene, indole, and benzotriazole nucleobases are reported. These nucleobase analogues are based on a similar scaffold but have different hydrogen-bond donor/acceptor groups that are expected to be oriented in the duplex minor groove. The unnatural base pairs do not appear to induce major structural distortions and are accommodated within the constraints of a B-form duplex. The differences between these unnatural base pairs are manifest only in the polymerase-mediated extension step, not in base-pair stability or synthesis. The benzotriazole self-pair is extended with an efficiency that is only 200-fold less than a correct natural base pair. The data are discussed in terms of available polymerase crystal structures and imply that further modifications may result in unnatural base pairs that can be both efficiently synthesized and extended, resulting in an expanded genetic alphabet.

Topics: Base Pairing; Benzofurans; Circular Dichroism; DNA; Hydrogen Bonding; Indoles; Kinetics; Nucleotides; Thiophenes; Triazoles