Supramolecular Radical Anions Triggered by Bacteria In†Situ for Selective Photothermal Therapy.

A supramolecular complex that can be selectively reduced to radical anions in situ by facultative anaerobic bacteria is reported. To this end, a water-soluble bifunctional monomer bearing perylene diimide was synthesized, and its supramolecular complex with cucurbit[7]uril was fabricated on the basis of host-guest complexation, which could be reduced to forming radical anions in the presence of E. coli. It was found that this supramolecular complex could display different ability of generating radical anions by facultative anaerobic and aerobic bacteria in terms of their various reductive abilities. The selective antibacterial activity of the supramolecular complex could be realized by the photothermal performance of the radical anions under near-infrared irradiation. It is anticipated that this method may lead to a novel bacteria-responsive photothermal therapy to regulate balance of bacterial flora.

Alkaloids from the Traditional Chinese Medicine ChanSu: synthesis-enabled structural reassignment of bufopyramide to bufoserotonin C.

A synthesis of putative bufopyramide has shown the structure assigned to the natural product to be incorrect. The spectroscopic data for the natural product bufopyramide matches that obtained from a synthetic sample of bufoserotonin C, confirming that the two natural products are not distinct, but instead the same compound.

Synthesis, structural, and biological evaluation of bis-heteroarylmaleimides and bis-heterofused imides.

Bis-2,3-heteroarylmaleimides and polyheterocondensed imides joined through nitrogen atoms of the N,N'-bis(ethyl)-1,3-propanediamine linker were prepared from substituted maleic anhydrides and symmetrical diamines in good to satisfactory yields and short reaction times using microwave heating. The novel molecules were shown to inhibit proliferation of human tumor cells (NCI-H460 lung carcinoma) and rat aortic smooth muscle cells (SMCs) with variable potencies. Compound 11a, the most potent one of the series, showed IC(50) values comparable to those observed for the leading molecule elinafide in both cell lines, but with a higher selectivity toward human tumor cells. Compound 11a affected G1/S phase transition of the cell cycle, showed in vitro DNA intercalating activity and in vivo antitumor activity. A thorough structural analysis of the 11a-DNA complex was also made by mean of NMR and computational techniques.

Microwave-assisted synthesis of N-substituted cyclic imides and their evaluation for anticancer and anti-inflammatory activities.

A number of N-substituted cyclic imides 3a-e, 5a-e, 7a-d, and 9a-e have been synthesized in very high yields, by condensation of various diacids 2, 4, 6, and 8 with different amines under microwave irradiation. These compounds were screened for anticancer and anti-inflammatory activities, and compounds 3c, 3e, 5c, 9c, and 9d exhibited anticancer activity against colon (COLO 205) cancer better than 5-fluorouracil and mitomycin-C, and compound 9b exhibited anti-inflammatory activity better than standard drug phenyl butazone.

N-aroyloxylthioxo-naphthalimides as DNA photocleavers of aroyloxyl oxygen radicals: synthesis, evaluation, and substituents' effect.

Novel N-Aroyloxylthioxo-naphthalimides as highly efficient 'time-resolved' DNA photocleavers of aroyloxyl radicals type were designed and synthesized. The substituents at the aroyloxyl moiety have an important and unusual influence on the DNA photocleavage, and DNA photodamages of the compounds were unusually not depended on the electronic effects of substituents on the corresponding oxygen-centered radicals. With AM1 semi-empirical quantum calculation, it was found that their photocleaving activities were correlated with the densities of electron clouds on the N-O bonds in the triplet state. N-(m-Dichloro-benzoyloxy)-thioxo-naphthalimide could photodamage DNA effectively at less than the concentration of 2 microM.

Investigations on the synthesis and properties of some N-[4-phenyl(2-pyrimidinyl)-1-piperazinyl]alkyl (hydroxyalkyl)-3,4-pyridinedicarboximides.

Synthesis of 2-substituted N-(4-phenyl-1 piperazinyl)propyl(butyl)- and N-2-hydroxy-3[4-phenyl(2-pyrimidinyl)-1-piperazinyl]propyl-6-methyl-3,4- pyridinedicarboximides [VI-XIV] is described. Some of them displayed depressive action on the central nervous system.

Synthesis and biological evaluation of a series of substituted N-alkoxyimides and -amides as potential atypical antipsychotic agents.

In a continuing program to discover antipsychotic agents with a reduced propensity toward extrapyramidal side-effects, a series of N-alkoxyimides and -amides was prepared. Evaluation of these compounds in vitro revealed affinities for D2, 5HT2 and 5HT1A receptors. Several members of the series displayed a profile indicative of potential antipsychotic activity in preclinical assays. The most potent compound in these assays, 7, also displayed possible effectiveness for the negative symptoms of schizophrenia. The synthesis of these compounds and details of their structure-activity relationships are described.