Neuritogenic activities of 1-alkyloxygenipins.

We designed 1-alkyloxygenipins with the aim of improving the stability of genipins based on the structural and electronic properties of genipins, and prepared 1-alkyloxygenipins and examined their neuritogenic activities in PC12h cells. All genipin-derivatives exhibited electronic properties similar to those of genipin and induced significant neurite outgrowth. These compounds will be classified as nitric oxide synthase (NOS) activators (neuritogenic active compounds) since their lowest unoccupied molecular orbital (LUMO)-energies are similar to that of tetrahydrobiopterin (H4B).

Comparison of the effects of percutaneous and intraduodenal administration of oxybutynin on bladder contraction and salivation in rabbits.

Aim: As only a few basic animal experiments have assessed the usefulness of percutaneous application of oxybutynin, we compared the effects of percutaneous application and intraduodenal injection of oxybutynin on urinary bladder contraction accompanied by micturition in conscious rabbits and salivation in anesthetized rabbits.

Methods: Bladder contractions were induced by continuous infusion of saline (2 mL/min) into the bladder. Salivary secretion was induced by pilocarpine (0.

Effects of 1-benzylxanthines on cyclic AMP phosphodiesterase 4 isoenzyme.

Based on our results regarding the structure-activity relationships of alkylxanthines and imidazo[2,1-i]purines as phosphodiesterase 4 (PDE4) inhibitors, we designed new 1-benzylxanthines and investigated their PDE4 inhibitory activities. 3,7-Dihydro-7-acetonyl-1-(2,4-dichlorobenzyl)-3-propyl-1H-purine-2,4-dione (2h) exhibited both more selective and more potent PDE4 inhibitory activity than rolipram and XT-611.

Simultaneous determination of 2-phenylbenzotriazole-type mutagens, PBTA-1 through -8, in river water by liquid chromatography-tandem mass spectrometry.

We describe a method for the simultaneous determination of eight kinds of phenylbenzotriazole-type mutagens (PBTA-1, -2, -3, -4, -5, -6, -7 and -8) in river water based on liquid chromatography-tandem mass spectrometry (LC/MS/MS). The application of dopant-assisted atmospheric pressure photoionization (APPI) for the detection of the PBTAs was studied. The APPI technique provided higher PBTA signal intensities than those obtained with an electrospray ionization (ESI) source, and the APPI method was used for the determination of the PBTAs.

Increased effects of MPDAX, a novel xanthine derivative, on antitumor activity of doxorubicin.

To clarify the effect of 1-methyl-3-propyl-7-N,N-dimethylpropylamide-xanthine (MPDAX) on doxorubicin (DOX) transport, we examined the efficacy of MPDAX as an amplifier of the antitumor activity of DOX in mice bearing tumors with different properties as to DOX transport across cell membranes. MPDAX significantly enhanced the DOX-induced antitumor activity on DOX-sensitive tumors. It is expected that the increase in antitumor activity caused by MPDAX contributes to the increased DOX concentration in tumors due to the MPDAX-induced change in DOX transport via the transporter expressed in sensitive tumor cells.

Cyclic AMP phosphodiesterase 4 isoenzyme inhibitory activity of (R)- and (S)-isomer of 7-methyl- or 8-alkyl-4,5,7,8-tetrahydroimidazo[2,1-i]- purin-5-one.

We investigated the structure-activity relationship of the (R)- and (S)-isomer of 7-methyl- and 8-alkyl-tetrahydroimidazo[2,1-i]purines for phosphodiesterase 4 (PDE4) inhibitors. (S)-8-Isopropyl-3,4-dipropyl-imizazo[2,1-i]purine (S)-2c exhibited both potent and selective PDE4 inhibitory activity.

Prostaglandin E2-mediated anabolic effect of a novel inhibitor of phosphodiesterase 4, XT-611, in the in vitro bone marrow culture.

Unlabelled: The mechanism of osteoblast formation by a novel PDE4 inhibitor, XT-611, was studied in the in vitro bone marrow culture system. The compound potentiated the osteoblast differentiation through accumulation of cyclic AMP after autocrine stimulation of EP4 receptor by PGE2 in pro-osteoblastic cells.

Introduction: We previously reported that inhibitors of phosphodiesterase (PDE)4 isoenzyme increase osteoblast formation in an in vitro bone marrow culture system and inhibit bone loss in animal osteoporosis models.

Levels and behavior of 2-phenylbenzotoriazole-type mutagens in the effluent of a sewage treatment plant.

We previously reported on the isolation and structural determination of five 2-phenylbenzotriazole (PBTA)-type mutagens (PBTA-1, PBTA-2, PBTA-3, PBTA-4 and PBTA-6) in blue rayon/cotton adsorbed substances collected from surface waters at sites located downstream of sewage treatment plants. We also noted that PBTA-1 and PBTA-2 were discharged from sewage treatment plants and subsequently diluted or decomposed while moving down the Yodo River system. However, it has not been investigated whether they are commonly discharged from sewage treatment plants into rivers.

Effects of xanthine derivatives on the influx and efflux of doxorubicin in P388 and DOX-resistant P388 leukemia cells.

It was reported that xanthine derivatives (caffeine and 1-methyl-3-propyl-7-butylxanthine) enhanced the antitumor activity of doxorubicin (DOX) with increasing DOX concentrations in tumors in vivo in our previous papers. In addition, these actions were found to be related to the inhibitory activity toward DOX efflux from tumor cells in vitro. In this study, we searched for novel biochemical modulators of DOX among 3-n-propylxanthines with functional groups at the 1- or 7-position by using an assay system for their inhibitory effect on DOX efflux from P388 leukemia and DOX resistant P388 leukemia (P388/DOX) cells.

Synthesis and cyclic AMP phosphodiesterase 4 isoenzyme inhibitory activity of heterocycle condensed purines.

To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP phosphodiesterase 4 (PDE4), a series of heterocycle [a]-, [b]-, [c,d]-, and [i]-condensed purines were designed and synthesized. Although all compounds did not display PDE1 and PDE3 inhibitory activities, several heterocycle [i]-condensed purines strongly inhibited PDE4. Especially, dl-3,4-dipropyl-8-methyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (dl-7c) exhibited comparable PDE4 inhibitory activity (IC(50)=1.

Mutagenicity of two 2-phenylbenzotriazole derivatives, 2-[2-(acetylamino)-4-(diethylamino)-5-methoxyphenyl]-5-amino- 7-bromo-4-chloro-2H-benzotriazole and 2-[2-(acetylamino)-4-(diallylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole and their detection in river water in Japan.

We recently detected five 2-phenylbenzotriazole (PBTA)-type mutagens (PBTA-1, PBTA-2, PBTA-3, PBTA-4 and PBTA-6) in concentrates from several rivers that flow in geographically different areas in Japan containing textile-related industries. On the basis of synthesis studies, these five PBTA derivatives were deduced to have originated from the corresponding dinitrophenylazo dyes, which are industrial chemicals used in textile dyeing, via reduction and chlorination. 2-[(2-Bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)-4-methoxyacetanilide (Color Index name Disperse Blue 291, CAS registry no.