Antiparasitic Peptide from the Ocean: Discovery, Synthesis and Structure-Activity Relationship Study

Millions of people die every year because of infectious diseases, and malaria is among the top five of the deadliest infectious disease. In 2018, malaria took more than four hundred thousand lives, and more than half of them are children under five years of age. Most malaria-affected parts of the world are also the home of the most underprivileged people. Seemingly, antimalarial drug discovery never achieved the attraction that it requires. Like malaria, another infectious disease that is not extensively explored by drug discovery campaigns is American trypanosomiasis or Chagas disease. More than a hundred years have passed since discovering the disease, and surprisingly only two drugs are clinically available; both are far from ideal. It is imperative to say that these disease areas require more attention from drug discovery researchers. Hence, my project focuses on drug discovery for these neglected diseases utilizing one of the most prolific sources for lead molecule generation, marine cyanobacteria. This thesis describes the discovery of an N-methylated peptide, naranjamide, from a marine cyanobacterium collected in the Portobelo National Park, Panama. The compound inhibited the growth of Trypanosoma cruzi and Plasmodium falciparum parasites. To confirm the structure and established its antiparasitic potential, I attempted to synthesize the molecule and found the synthetic version to inhibit both T. cruzi and P. falciparum parasite with IC50 values of 9.2 μM and 2.8 μM, respectively. Later, a series of non-methylated analogs were synthesized, which are found to be malaria selective. A more detailed study is required to establish a complete structure-activity relationship

Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice

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.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

GABA mediated response of aqueous, ethanol andethyl acetate extracts of Dicranopteris linearis leaf inSwiss Albino mice

Introduction: The objective of the study was to assess the potential of the leaf of Dicranopteris linearis in altering the CNS functions with three different extracts; aqueous, ethanol and ethyl acetate.Methods: To evaluate and compare the activities Morris maze, elevated plus maze (EPM),open field, hole cross and head dip tests were performed and many behavioral parameters wereobserved. The forced swim in Morris water maze analyzed the depression of rodents in termsof inability to self-rescue. Alongside, hole cross and open field tests assessed the inhibition oflocomotor activities. Moreover, EPM test screened the anxiolytic potential while the head dippinghole board test supported the previous experiments by evaluating both sedative, depressive andanxiolytic potentials of the extracts.Results: The results showed that the ethanol extract significantly suppressed CNS activity byreducing number of locomotor activities and increasing the stability phase (in EPM and Morrismaze) supporting mild sedation, depression and anxiolysis. Furthermore, the ethyl acetate extractalso possessed moderate to high potential in reducing locomotor activities depending on gradientdoses. Results were compared with control group and found statistically significant.Conclusion: As this plant mimic the activity of a gamma-aminobutyric acid (GABA) agonist, itcan be concluded that the plant may have GABA mediated involvement in central nervous system.However, the responsible compounds for these activities are yet to be investigated and this maypotentiate a new source of drug development

Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice

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 receptorspecific 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 compoundsMarine 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 receptorspecific 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 compound

A comparative study of the antioxidant, antimicrobial, cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

Objective: To investigate the antioxidant, antimicrobial, cytotoxic and thrombolytic property of the fruits and leaves of Spondias dulcis (S. dulcis). Methods: Methanolic extracts of fruits and leaves of S. dulcis were partitioned with chloroform and dichloromethane. The antioxidant potential of the crude extract and partitioned fractions were evaluated in terms of total phenolic content, total flavonoid content, DPPH radical scavenging potential, reducing potential and total antioxidant capacity by specific standard procedures. The antimicrobial activity was evaluated using disc diffusion method. The cytotoxicity was evaluated by using brine shrimp lethality bioassay and compared with vincristine sulfate. The thrombolytic activity was compared with streptokinase. Results: The methanolic fruit extract exhibited the highest phenolic content, flavonoid content and antioxidant capacity, among the other extracts, with the highest DPPH radical scavenging activity at a concentration of 10 μg/mL (IC: 1.91 μg/mL) and maximum reducing power at a concentration of 100 μg/mL (EC: 3.58 μg/mL). Though all extract showed moderate antimicrobial activity against the bacterial strains, weak or no activity against fungus. The range of LC value of all extracts was 1.335-14.057 μg/mL which was far lower than the cut off index for cytotoxicity. All extracts exhibited statistically significant (

GABA mediated response of aqueous, ethanol and ethyl acetate extracts of Dicranopteris linearis leaf in Swiss Albino mice

Introduction: The objective of the study was to assess the potential of the leaf of Dicranopteris linearis in altering the CNS functions with three different extracts; aqueous, ethanol and ethyl acetate.Methods: To evaluate and compare the activities Morris maze, elevated plus maze (EPM),open field, hole cross and head dip tests were performed and many behavioral parameters wereobserved. The forced swim in Morris water maze analyzed the depression of rodents in termsof inability to self-rescue. Alongside, hole cross and open field tests assessed the inhibition oflocomotor activities. Moreover, EPM test screened the anxiolytic potential while the head dippinghole board test supported the previous experiments by evaluating both sedative, depressive andanxiolytic potentials of the extracts.Results: The results showed that the ethanol extract significantly suppressed CNS activity byreducing number of locomotor activities and increasing the stability phase (in EPM and Morrismaze) supporting mild sedation, depression and anxiolysis. Furthermore, the ethyl acetate extractalso possessed moderate to high potential in reducing locomotor activities depending on gradientdoses. Results were compared with control group and found statistically significant.Conclusion: As this plant mimic the activity of a gamma-aminobutyric acid (GABA) agonist, itcan be concluded that the plant may have GABA mediated involvement in central nervous system.However, the responsible compounds for these activities are yet to be investigated and this maypotentiate a new source of drug development

Fundamentals and Applications of Chitosan

International audienceChitosan is a biopolymer obtained from chitin, one of the most abundant and renewable material on Earth. Chitin is a primary component of cell walls in fungi, the exoskeletons of arthropods, such as crustaceans, e.g. crabs, lobsters and shrimps, and insects, the radulae of molluscs, cephalopod beaks, and the scales of fish and lissamphibians. The discovery of chitin in 1811 is attributed to Henri Braconnot while the history of chitosan dates back to 1859 with the work of Charles Rouget. The name of chitosan was, however, introduced in 1894 by Felix Hoppe-Seyler. Because of its particular macromolecular structure, biocompatibility, biode-gradability and other intrinsic functional properties, chitosan has attracted major scientific and industrial interests from the late 1970s. Chitosan and its derivatives have practical applications in food industry, agriculture, pharmacy, medicine, cos-metology, textile and paper industries, and chemistry. In the last two decades, chito-san has also received much attention in numerous other fields such as dentistry, ophthalmology, biomedicine and bio-imaging, hygiene and personal care, veterinary medicine, packaging industry, agrochemistry, aquaculture, functional textiles and cosmetotextiles, catalysis, chromatography, beverage industry, photography, wastewater treatment and sludge dewatering, and biotechnology. Nutraceuticals and cosmeceuticals are actually growing markets, and therapeutic and biomedical products should be the next markets in the development of chitosan. Chitosan is also the N. Morin-Crini (*) · Laboratoire Chrono-environnement, UMR 6249, UFR Sciences et Techniques