Search

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Context: Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple fruits, popularly known as 'jambolão' or 'jambolan'. In folk medicine, this plant is used for the treatment of diabetes and inflammatory conditions. Objective: We investigated the antinociceptive effect of ethanol extract (EE) from S. cumini leaves on orofacial nociception. Material and methods: The antinociceptive effects of the EE obtained from the leaves of S. cumini were evaluated in mice using formalin- and glutamate-induced orofacial nociception. Results: ESI-MS/MS analyses demonstrated that major constituents in the analyzed samples coincided with the mass of the phenolic acids and flavonoids. In pharmacological approach, pre-treatment with EE (100, 200, or 400 mg/kg, p.o.) significantly reduced ( p < 0.05 or p < 0.01) the percentage of paw licks time during phase 2 (43.2, 47.1, and 57.4%, respectively) of a formalin pain test when compared to control group animals. This effect was prevented by pretreatment with glibenclamide and NG-nitro- l-arginine ( l-NOARG). The extract, all doses, also caused a marked inhibition ( p < 0.01 or p < 0.001) of glutamate-induced orofacial nociception (38.8, 51.7, and 54.7%) when compared with the control group. No effect was observed with the rota-rod model. Conclusions: We can suggest that the antinociceptive effect of the EE is mediated by peripheral mechanisms, possibly involving KATP channels and the nitric oxide pathways. These effects appear to be related to the presence of flavonoids compounds, such as quercetin. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the hypotensive, vasorelaxant and antihypertensive effects elicited by the hydroalcohol extract from the fruits of Syzygium cumini (EHSCF) in non-anesthetized rats. Methods: The rats were anesthetized and polyethylene catheters were inserted into the lower abdominal aorta and into the inferior vena cava for blood pressure measurements and administration of drugs. After a recovery period of 24 h, EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg, i.v.) was administered in non-anesthetized rats. The mean arterial pressure and the heart rate were recorded. To investigate the effects of extract, doses EHSCF were administered after pretreatment with L-NAME, atropine, indomethacin, and hexamethonium. For measurement of isometric tension, a concentration-response curve was obtained after Phenylephrine and KCl (80 mM) pre-contractions. The bioactive extract was analyzed via mass spectrometry (MS) fingerprinting using direct electrospray ionization mass spectrometry (ESI-MS). Results: EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg) induced hypotension (-15 ± 1, -14 ± 1, -15 ± 1, -13 ± 1, -11 ± 1 and -13 ± 2%) and bradycardia (-6 ± 1, -5 ± 1, -6 ± 1, -14 ± 1, -8 ± 1 and -10 ± 2%) in normotensive rats. These responses were attenuated by pre-treatment with L-NAME, indomethacin, hexamethonium or atropine. In phenylephrine, pre-contracted mesenteric rings, EHSCF-induced relaxation (Emax = 54.6 ± 4.5% and pD2 = 2.7 ± 0.1) that were affected by endothelium removal. EHSCF caused relaxant effect of KCl (80 mM) pre-contracted rings (Emax = 100 ± 0.2% and pD2 = 2.2 ± 0.1). This effect was not changed in denuded rings. A single oral administration of the extract reduced significant mean arterial pressure in spontaneously hypertensive rats. ESI-MS/MS analyses of EHSCF demonstrated that the major constituents of the analyzed samples coincided with the mass of the malic, gallic, caffeic and ferulic acids. Conclusion: The results suggest that EHSCF induces hypotension probably due to a decrease in peripheral resistance, mediated by the endothelium. Bradycardia may be due to indirect cardiac muscarinic activation. The extract also causes an antihypertensive effect. [ABSTRACT FROM AUTHOR]

Background: Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine., Methods: Mice were treated with LQM01 (5, 10, 25 or 50 mg/kg, i.p.), vehicle (0.9% saline i.p.) or a standard drug. The mice were subjected to carrageenan-induced pleurisy, abdominal writhing induced by acetic acid, the formalin test and the hot-plate test. The model of non-inflammatory chronic muscle pain induced by saline acid was also used. Mice from the chronic protocol were assessed for withdrawal threshold, muscle strength and motor coordination. LQM01 or vehicle treated mice were evaluated for Fos protein., Results: LQM01 inhibits TNF-α and IL-1β production, as well as leukocyte recruitment during inflammation process. The level of IL-10 in LQM01-treated mice increased in pleural fluid. In addition, LQM01 decreased the nociceptive behavior in the acetic acid induced writhing test, the formalin test (both phases) and increased latency time on the hot-plate. LQM01 treatment also decreased mechanical hyperalgesia in mice with chronic muscle pain, with no changes in muscle strength and motor coordination. LQM01 reduced the number of Fos positive cells in the superficial dorsal horn. This compound exhibited antioxidant properties in in vitro assays., Conclusions: LQM01 has an outstanding anti-inflammatory and analgesic profile, probably mediated through a reduction in proinflammatory cytokines release, increase in IL-10 production and reduction in neuron activity in the dorsal horn of the spinal cord in mice., General Significance: Beneficial effects of LQM01 suggest that it has some important clinical features and can play a role in the management of 'dysfunctional pain' and inflammatory diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)