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221.
Simone Giovannuzzi Chad S. Hewitt Alessio Nocentini Clemente Capasso Daniel P. Flaherty Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):333
Coumarins are known to act as prodrug inhibitors of mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) but they were not yet investigated for the inhibition of bacterial α-CAs. Here we demonstrate that such enzymes from the bacterial pathogens Neisseria gonorrhoeae (NgCAα) and Vibrio cholerae (VchCAα) are inhibited by a panel of simple coumarins incorporating hydroxyl, amino, ketone or carboxylic acid ester moieties in various positions of the ring system. The nature and the position of the substituents in the coumarin ring were the factors which strongly influenced inhibitory efficacy. NgCAα was inhibited with KIs in the range of 28.6–469.5 µM, whereas VchCAα with KIs in the range of 39.8–438.7 µM. The two human (h)CA isoforms included for comparison reason in the study, hCA I and II, were less prone to inhibition by these compounds, with KIs of 137–948.9 µM for hCA I and of 296.5–961.2 µM for hCA II, respectively. These findings are relevant for discovering coumarin bacterial CA inhibitors with selectivity for the bacterial over human isoform, with potential applications as novel antibacterial agents. 相似文献
222.
Renato Capasso Nicola S. Iacobellis Antonio Bottalico Giacomino Randazzo 《Phytochemistry》1984,23(12):2781-2784
The structure-toxicity relationships of phomenone were studied on cuttings and seedlings of tomato, and on larvae of brine shrim. Four derivatives prepared by chemical modification of phomenone were tested in comparison with PR-toxin. The toxicity to tomato cuttings (wilting and necroses of leaflets) appeared to be dependent on the integrity of the phomenone molecule, as any structural modification markedly reduced or completely abolished its phytotoxicity. By contrast, the toxicity to tomato seedlings (growth inhibition of shoots and rootlets) and to brine shrimp (larvae mortality) suggested a role for the epoxy rings in eremophilane molecules, which was enhanced by acetylation, as demonstrated by the progressive loss of activity for the sequence PR-toxin, phomenone and 9-methoxy- 6,7-de-epoxyphomenone. 相似文献
223.
Rat isolated intestine incubated in Krebs solution converted exogenous [14C]-arachidonic acid into products that chromatographed with prostaglandins, leukotriene B4 and 5-hydroxy-eicosatetraenoic acid. Accumulation of these products was increased by the laxative ricinoleic acid (0.34 mM) or the calcium ionophore A23187 (7.6 microM). In the presence of the calcium antagonists TMB-8 (0.43 microM) or verapamil (0.2 microM) the mean effects of ricinoleic acid or the calcium ionophore were smaller. Stimulation of arachidonic acid metabolism by ricinoleic acid therefore seems likely to involve a calcium-dependent mechanism. 相似文献
224.
Global stability results for a generalized Lotka-Volterra system with distributed delays 总被引:3,自引:0,他引:3
The paper contains an extension of the general ODE system proposed in previous papers by the same authors, to include distributed time delays in the interaction terms. The new system describes a large class of Lotka-Volterra like population models and epidemic models with continuous time delays. Sufficient conditions for the boundedness of solutions and for the global asymptotic stability of nontrivial equilibrium solutions are given. A detailed analysis of the epidemic system is given with respect to the conditions for global stability. For a relevant subclass of these systems an existence criterion for steady states is also given.Work supported by the Special Program Control of Infectious Diseases, C.N.R. and by the M.P.I., Italy 相似文献
225.
A Capasso P Cretì B De Petrocellis P P De Prisco E Parisi 《Biochemical and biophysical research communications》1988,154(2):758-764
The adenylate cyclase of the sea urchin egg is stimulated by dopamine in the presence of GTP. The enzyme activity is strongly enhanced when Gpp (NH)p is substituted for GTP, or after cholera toxin treatment. Gramine, an indolamine derivative, brings about non-competitive inhibition of the dopamine-stimulated adenylate cyclase activity. Pertussis toxin causes an attenuation of the gramine-induced inhibition of adenylate cyclase. These results show that dopamine and indolamine derivatives partecipate in the regulation of the adenylate cyclase activity of the sea urchin egg. 相似文献
226.
Extensive digestion of Na+,K(+)-ATPase by specific and nonspecific proteases with preservation of cation occlusion sites. 总被引:6,自引:0,他引:6
J M Capasso S Hoving D M Tal R Goldshleger S J Karlish 《The Journal of biological chemistry》1992,267(2):1150-1158
This paper extends our recent report that renal Na+,K(+)-ATPase is digested by trypsin in the absence of Ca2+ and presence of Rb+ ions to a stable 19-kDa fragment and smaller membrane-embedded fragments of the alpha chain and essentially intact beta chain. These are referred to as "19-kDa membranes." Occlusion of both Rb+ (K+) or Na+ ions is preserved, but ATP-dependent functions are lost (Karlish, S. J. D., Goldshleger, R., and Stein, W. D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4566-4570). We now show that extensive digestion with nonselective fungal proteases (Pronase and proteinase K) alone, in combination, or after tryptic digestion can remove up to 70% of membrane protein without destroying Rb+ occlusion. In the most heavily digested membranes, the 19-kDa fragment or a slightly shorter 18.5-kDa fragment and smaller fragments of the alpha chain remain, whereas the beta chain is largely digested, leaving smaller membrane-embedded fragments (13-15 kDa). For either trypsin or Pronase digestion, preservation of Rb+ occlusion and the specific fragmentation pattern is observed only in the absence of divalent metal ions (Mg2+ or Ca2+) and presence of either Rb+ or Na+ or congener ions. Tryptic digestion at pH 7.0 can split the beta chain into two fragments of approximately 50 and 16 kDa joined by an S-S bridge. The 16-kDa fragment is protected against further digestion by the presence of Rb+ ions, but probably is not directly involved in occluding cations. Tryptic 19-kDa membranes show a clear and reproducible fragmentation pattern in which all predicted membrane segments are identifiable. Families of fragments from 19-kDa membranes, including seven peptides of 7.6-11.7 kDa, have been separated by size-exclusion high performance liquid chromatography, concentrated, and resolved on 16.5% Tricine gels. N-terminal sequences of the different fragments have been determined after transfer to polyvinylidene difluoride paper. The most interesting findings are as follows. (a) Whereas the 19-kDa tryptic fragment begins at Asn831 as reported previously, the 18.5-kDa Pronase fragment begins at Thr834. (b) Fragments in tryptic 19-kDa membranes of 7.6-11.7 kDa begin at Asp68, Ile263, and Gln737, respectively. These include all putative transmembrane segments other than those in the 19-kDa fragment. (c) A Pronase fragment of 7.8 kDa begins at Thr834, i.e. apparently the 19-kDa fragment has been partially cut, without loss of Rb+ occlusion. (d) Tryptic 16- and approximately 50-kDa fragments of the beta chain begin at Ala5 and Gly143, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
227.
The present study examined interaction between dexamethasone (DEX) and morphine on the locomotor activity in groups of mice by using the activity cage test. Morphine administration (30-75-150 mg/kg, ip) induced a dose-related increase of the locomotor activity of mice, whereas DEX per se (0.1-1.0-10 mg/kg, ip) did not modify the activity of control mice. Pretreatment of mice with DEX 0.1 mg did not alter the hyperactivity produced by the three doses of morphine. In contrast, DEX administered at 1.0 mg reduced the morphine effects on locomotor activity, whereas DEX at 10 mg potentiated the morphine hypermotility. Our results suggest that DEX may play an important regulatory role on the central effects of morphine through a differential modulation of brain excitability systems. 相似文献
228.
F. Capasso N. Mascolo G. Autore M.R. Duraccio 《Prostaglandins & other lipid mediators》1983,26(4):557-562
The effect of aloin and 1,8 dioxyanthraquinone on the release of prostaglandin-like material (PG) from rat isolated colon has been investigated. Orally administered aloin and 1,8 dioxyanthraquinone stimulates PG production by subsequently isolated segments of colon. Indomethacin was able to prevent this increased production of PG. These results suggest that the laxative properties of aloin and 1,8 dioxyanthraquinone may depend, at least in part, on increased prostaglandin synthesis by the intestinal tissue. 相似文献
229.
Capasso R Cristinzio G Evidente A Visca C Ferranti P Del Vecchio Blanco F Parente A 《Phytochemistry》1999,50(5):703-709
Elicitin 172, an acid protein with elicitor activity, has been isolated in true form from culture filtrates of Phytophthora nicotianae, the causal agent of crown and root rot of tomato (Lycopersicon esculentum). The M(r) (10,349 +/- 1) of the purified protein, determined by ES-MS, is identical to that calculated for parasiticein using the mean isotopic composition and assuming the occurrence of three disulfide bridges. The primary structure of elicitin 172, determined using also MALDI-MS experiments, shows complete identity with parasiticein, with elicitin 310 and a cloned elicitin gene from P. parasitica (= P. nicotianae), confirming conservation of the elicitin sequence within a single species. The protein induces necrosis (hypersensitive reaction) on tobacco, but no symptoms on tomato, when applied on the leaves. Tomato pretreated with elicitin 172 was affected by P. nicotianae, as well as by the phytotoxic aggregates, naturally occurring with the elicitin in the non permeated dialysis fraction of culture filtrates. Finally, the elicitin induce protection of capsicum (Capsicum annuum) and vegetable marrow (Cucurbita pepo) from P. capsici. 相似文献
230.
F Borrelli E Mereto F Capasso P Orsi D Sini A A Izzo B Massa M Boggio N Mascolo 《Life sciences》2001,69(16):1871-1877
Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara. 相似文献