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Context Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. Objective To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. Materials and methods Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests. Results 2064H was shown to bind to the serotonin 2C (5-HT2C) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [3H]-mesulergine with an IC50 of 179 ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first min of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test. Discussion and Conclusion Overall, manipulating the 5-HT2C receptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds.

A convergent 5-step synthesis (LLS) of illudalic acid allows for concise preparation of analogues for pharmacological evaluation.

The ethanol leaf extract of Cymbidium aloifolium (L.) was evaluated for its analgesic and antiinflammatory activities. The extract, at the dose of 200 and 400 mg kg(-1) body weight, exerted the analgesic activity by observing the number of abdominal contractions and anti-inflammatory activity against Carrageenin induced paw edema in mice by measuring the paw volume. The ethanolic extract of Cymbidium aloifolium (L.) showed statistically significant (p < 0.05) reduction of percentage of writhing of 33.57 and 61.31% at 200 and 400 mg kg(-1) oral dose, respectively, when compared to negative control. The Ethanolic plant extract also showed significant (p < 0.05) dose dependent reduction of mean increase of formation of paw edema. The results of the experiment and its statistical analysis showed that the ethanolic plant extract had shown significant (p < 0.05) dose dependent analgesic and anti-inflammatory activities when compared to the control.

The present study was designed to compare the antioxidant, antimicrobial and thrombolytic effects of the Lannea coromandelica bark and leave extracts. After the initial phytochemical screening, the ethanolic fractions of the L. coromandelica bark and leaves were partitioned by solvents of different polarity. Methods used to evaluate the antioxidant potential of the extracts were total phenolic content, total flavonoid content, free radical scavenging capacity, total antioxidant capacity and reducing power assay. Total phenol and total flavonoid contents were found to be the highest for bark and leaves in the ethyl acetate fraction and lowest in the n-Hexane fraction. In DPPH free radical scavenging test, the lowest IC 50 value was found in the ethyl acetate fraction of the bark and leaf, resulting IC 50 value of 3.8±0.14 μg/ml and 6±0.32 μg/ml respectively. In the same vein, ethyl acetate fraction of both leaf and bark showed the highest antioxidant capacity and reducing power. Reducing power of both bark and leaves were found to be concentration dependent and most prominent was observed with the fractions of higher polarity both in case of bark and in case of leaves. Furthermore, the leaf extracts produced moderate antimicrobial activity whereas the bark extracts showed weak antimicrobial activity. Dichloromethane fraction of leaf showed the most potent antimicrobial activity with zone of inhibition ranging from 8 mm to 21 mm at a dose of 400µg/disc and 10 mm to 23 mm at a dose of 800µg/disc. In addition, extracts from both parts of L. coromandelica produced good thrombolytic activity compared with streptokinase.

PHPT1 is a protein histidine phosphatase that has been implicated in several disease pathways, but the chemical tools necessary to study the biological roles of this enzyme and investigate its utility as a therapeutic target have yet to be developed. To this end, the discovery of PHPT1 inhibitors is an area of significant interest. Here, we report an investigation of illudalic acid and illudalic acid analog‐based inhibition of PHPT1 activity. Four of the seven analogs investigated had IC50 values below 5 μM, with the most potent compound (IA1‐8H2) exhibiting an IC50 value of 3.4±0.7 μM. Interestingly, these compounds appear to be non‐covalent, non‐competitive inhibitors of PHPT1 activity, in contrast to other recently reported PHPT1 inhibitors. Mutating the three cysteine residues to alanine has no effect on inhibition, indicating that cysteine is not critical for interactions between inhibitor and enzyme.

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