In this work, we discuss the characterization and diversity analysis of 354 natural products (NPs) from Panama, systematically analyzed for the first time. The in-house database was compared to NPs from Brazil, compounds from Traditional Chinese Medicine, natural and semisynthetic collections used in high-throughput screening, and compounds from ChEMBL. An analysis of the "global diversity" was conducted using molecular properties of pharmaceutical interest, three molecular fingerprints of different design, molecular scaffolds, and molecular complexity. The global diversity was visualized using consensus diversity plots that revealed that the secondary metabolites in the Panamanian flora have a large scaffold diversity as compared to other composite databases and also have several unique scaffolds. The large scaffold diversity is in agreement with the broad range of biological activities that this collection of NPs from Panama has shown. This study also provided further quantitative evidence of the large structural complexity of NPs. The results obtained in this study support that NPs from Panama are promising candidates to identify selective molecules and are suitable sources of compounds for virtual screening campaigns.

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We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

Bioassay-guided fractionation of the chloroform and ethanol extracts of Tovomita longifolia leaves using cytotoxic and antimicrobial assays resulted in the isolation of four new benzophenones, (E)-3-(2-hydroxy-7-methyl-3-methyleneoct-6-enyl)-2,4,6-trihydroxybenzophenone (1), (E)-3-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-2,4,6-trihydroxybenzophenone (2), 8-benzoyl-2-(4-methylpenten-3-yl)chromane-3,5,7-triol (3), and 5-benzoyl-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthene-6,8-diol (4), and two known benzophenones, 4-geranyloxy-2,6-dihydroxybenzophenone (5) and 3-geranyl-2,4,6-trihydroxybenzophenone (6). The structures of 1-4 were established by spectroscopic means and by molecular modeling calculations. Compounds 1 and 3-5 demonstrated cytotoxic activities against breast (MCF-7), central nervous system (SF-268), and lung (H-460) human cancer cell lines, while compounds 3-6 showed antimicrobial activity against Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella gallinarum, and Staphylococcus aureus.

Bioassay-guided fractionation of the CH(2)Cl(2) extract of the leaves of Marila pluricostata led to the isolation of 17 naturally occurring 4-phenylcoumarins, three of them, 5-hydroxy-8,8-dimethyl-4-phenyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (1), 5-hydroxy-8,8-dimethyl-4-phenyl-6-propionyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (2), and 5,7-dihydroxy-8-(3-methylbut-2-enyl)-4-phenylchromen-2-one (3), are new natural compounds; the remaining (4-17) are known mammea-type coumarins. Their structures were established by spectroscopic means. All compounds were tested in cytotoxicity assays against the MCF-7, H-460, and SF-268 human cancer cell lines.

Chemoinformatic analysis was used to characterize a compound database of natural products from Panama and other reference collections. Data mining allowed to compare drug-likeness properties with public and commercial software and to achieve a statistical analysis of the physicochemical properties. Visualization of the chemical space in 3D indicates a high structural similarity. Molecular flexibility and complexity were evaluated using 2D descriptors, whereas the molecular scaffold was obtained using the Murcko method, and these showed few differences between the explored data set. In this chapter, we also present and discuss an example of the application of the chemoinformatic approach using the concept of modeling the activity landscape to study the structure-activity relationships (SARs) of compounds with activity against Plasmodium falciparum.

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In this study, the furofuran lignan (+)-diayangambin [tetrahydro-1,4-bis(3,4,5-trimethoxyphenyl)-(1 R)-1alpha,3abeta,4alpha,6abeta-1 H,3 H-furo [3,4- c]furan] was evaluated in vitro and in vivo for its immunomodulatory and anti-inflammatory efficacy. Human mononuclear cell proliferation was inhibited by diayangambin with an IC 50 value of 1.5 (0.5 - 2.8) microM. In addition, the compound reduced for 40.8 % prostaglandin E 2 generation in stimulated RAW 264.7 macrophage cell line at 10 microM. In vivo, a clear reduction of ear swelling was observed when diayangambin (40 mg/kg) was administered orally to 2,4-dinitrofluorobenzene-treated mice. The inhibition of swelling was associated with a reduction of leukocyte infiltration determined as myeloperoxidase activity. In the carrageenan mouse paw edema model, diayangambin significantly suppressed inflamed paw volume and prostaglandin E 2 levels. Our findings indicate the potential interest of diayangambin in the treatment of immune and inflammatory responses.