A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good activity without significant toxic effects. The compound with the highest activity was used for an in vivo assay with Leishmania amazonensis.

Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species.

The present study investigated gossypetin 3,7,8,4′-tetra-O-methyl ether (1) and kaempferol 3,7-di-O-methyl ether (3) which showed significant leishmanicidal activity without toxic effects to host cells.

The marine environment is an extraordinary reservoir of bioactive natural products, many of which exhibit chemical and structural features not found in terrestrial natural products. In this regard, the aim of this study was to investigate the possible antinociceptive and anti-inflammatory activities of a crude methanolic extract of the red alga Bryothamnion triquetrum (BT-MeOH) in murine models. Groups of Swiss mice of both sexes (25–30 g) were used throughout the experiments. The potential antinociceptive of BT-MeOH was evaluated by means of the following tests: acetic acid-induced writhing, hot-plate test and glutamate- and formalin-induced nociception. The anti-inflammatory activity of BT-MeOH was investigated using the zymosan A-induced peritonitis test. The tests were conducted using 100 mg/kg (p.o.) BT-MeOH, 33.3 mg/kg (p.o.) dipyrone, 35.7 mg/kg (p.o.) indomethacin and 5.7 mg/kg (s.c.) morphine. The extract and all standard drugs were administered 40 min before the nociceptive/inflammatory stimulus. In the acetic acid-induced writhing test, BT-MeOH and dipyrone inhibited the nociceptive response by 55.9% (22.2 ± 2.0 writhings; p < 0.01) and 80.9% (9.6 ± 2.1 writhings; p < 0.01). In the hot-plate test, BT-MeOH did not increase the latency time of the animals in the time evaluated. In addition, BT-MeOH inhibited glutamate-induced nociception by 50.1%. While BT-MeOH did not inhibit the neurogenic phase in formalin-induced nociception, the inflammatory phase was inhibited by 53.1% (66.8 ± 14.2 s; p < 0.01). Indomethacin inhibited the inflammatory phase by 60.2% (56.8 ± 8.7 s; p < 0.01). In the zymosan-induced peritonitis test, BT-MeOH inhibited 55.6% (6.6 ± 0.2 × 106 leukocytes/mL; p < 0.01) of leukocyte migration, while indomethacin inhibited 78.1% (3.2 ± 0.1 × 106 leukocytes/mL; p < 0.01). Based on the results obtained in this study, we conclude that BT-MeOH has peripheral antinociceptive and anti-inflammatory activities. However, more studies need to be conducted to confirm these properties.

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In this study, we investigated the antinociceptive effect of 7-methoxyflavone (7MF) in mice using the following tests: acetic acid-induced writhing, glutamate- and formalin-induced nociception and hotplate. 7MF (30, 50, 100 and 300 μmol/kg, i.p.) reduced the number of writhes, with ID₅₀ = 82.5 ± 11.7 μmol/kg and E max = 58.4%. 7MF treatment (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin pain response (65.6%) and did not decrease the nociceptive response in the inflammatory phase. In addition, in glutamate-induced nociception, 7MF inhibited 26% of the nociceptive answer. On the other hand, 7MF did not increase the latency time of the animals in the hotplate test. These results suggest that 7MF has peripheral antinociceptive activity.

No abstract

Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. In this study was evaluated in vitro leishmanicidal activity of 2-N,N'-dialkylamino-1,4-naphthoquinone derivatives, covering a series of fourteen 2-N-morpholino-, 2-N-thiomorpholino, 2-N-piperidino, 2-N-(N-methyl)-piperazino naphthoquinones (1a-n) derived from nor-lapachol and lawsone, belong to some other di-alkyaminoderivatives. At the cytotoxicity assay on peritoneal macrophages, the compounds possessing larger alkyl groups and N-methyl-piperazino moiety (1d, 1h, 1i and 1k), showed toxic effects similar to the standard drug used pentamidine. However, the other compounds of the series showed no deleterious effect on the host cell. Meanwhile, these cytotoxic derivatives (1d, 1h and 1i) had pronounced leishmanicidal activity against L. amazonensis promastigotes, and treatments with six other compounds (1d, 1e, 1f, 1h, 1k and 1n) had significant effect leishmanicidal against L. chagasi promastigotes. In the assay against L. chagasi amastigotes, eight compounds (1a, 1b, 1c, 1d, 1h, 1i, 1k and 1m) showed significant activity. Moreover, the compounds (1a, 1b, 1c, and 1m) showed effect against amastigotes of L. chagasi and not being toxic to the host cell. These data show the derivatives as promising substances for research leishmanicidal activity.