The future of diagnosis in clinical neurosciences: Comparing multiple sclerosis and schizophrenia.

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.

Furoquinoline alkaloids of Ertela (Monnieria) trifolia (L.) Kuntze from the Suriname rainforest.

7-(2'-Hydroxy-3'-chloroprenyloxy)-4,8-dimethoxyfuroquinoline (1) and 6-(2'-hydroxy-3'-chloroprenyloxy)-4,7-dimethoxyfuroquinoline (2), together with ten known compounds, have been isolated from the aerial parts of Ertela (Monnieria) trifolia (L.) Kuntze. All the isolates were tested for antiproliferative activity against the A2780 human ovarian cancer cell line.

Ipomoeassin F, a new cytotoxic macrocyclic glycoresin from the leaves of Ipomoea squamosa from the Suriname rainforest.

A new cytotoxic macrocyclic glycoresin, ipomoeassin F (6), has been isolated from the leaves of Ipomoea squamosa. The structure was elucidated by the interpretation of spectral data. Compound 6 was strongly active in the A2780 (human ovarian cancer cell line) assay with an IC(50) value of 0.036 microM.

Cytotoxic diterpenoids from two lianas from the Suriname rainforest.

Bioassay-guided fractionation of the MeOH and EtOAc fractions of extracts of two lianas collected in Suriname has led to the isolation of five new diterpenoids, humirianthone 1, 1-hydroxy-humirianthone 2, 15R-humirianthol 3, patagonol 4, and patagonal 5, and the five known diterpenoids, humirianthol 7, annonalide 8, acrenol 9, icacinol 10, and the oxidized annonalide 11. All 10 diterpenoids showed cytotoxic activity against the A2780 human ovarian cancer cell line, and compounds 1, 3, 8, and 9 also showed activity against phytopathogenic fungi.

Ipomoeassins A-E, cytotoxic macrocyclic glycoresins from the leaves of Ipomoea squamosa from the Suriname rainforest.

The new glycoresins, ipomoeassins A-E (1-5), have been isolated from the leaves of Ipomoea squamosa. The structures were elucidated by spectroscopic analyses and chemical transformations. The absolute configurations of C-5 (ipomoeassins 3-5) and C-11 (ipomoeassins 1 and 2) were determined by their derivatives with (R)- and (S)-MPA. All the isolates were active in the A2780 human ovarian cancer cell line assay, and 4 showed the highest activity with an IC(50) value of 35 nM.

New eudesmane derivatives from Melampodium camphoratum from the Suriname rainforest.

Bioassay-guided fractionation of an EtOAc extract of the leaves of Melampodium camphoratum using an assay for inhibitors of the degradation of hemin resulted in the isolation of six new eudesmane sesquiterpenes (1-6) and the known 6-epi-beta-verbesinol coumarate (7). The structures of compounds 1-6 were established as 6alpha-(4'-O-methyl-7'E-coumaryloxy)eudesm-4(14)-ene (1), 6alpha-({4'-O-stearyl}-7'E-coumaryloxy)eudesm-4(14)-ene (2), 6alpha-({4'-O-palmityl}-7'E-coumaryloxy)eudesm-4(14)-ene (3), 6alpha-({4'-O-[9' 'Z-hexadecenoyl]}-7'E-coumaryloxy)eudesm-4(14)-ene (4), 6alpha-(7'Z-coumaryloxy)eudesm-4(14)-ene (5), and 6alpha-({4'-acetoxy}-7'Z-coumaryloxy)eudesm-4(14)-ene (6). Compounds 1-4 showed weak activity in the hemin degradation assay, while compounds 5-7 were inactive.

A novel cytotoxic guttiferone analogue from Garcinia macrophylla from the Suriname rainforest.

Bioassay-guided fractionation of the EtOAc extract of the twigs of Garcinia macrophylla from Suriname produced the known benzophenone, guttiferone A (1), and a new guttiferone analogue, guttiferone G (2). Friedelin was also isolated. The structures of compounds 1 and 2 were elucidated using 1D and 2D NMR spectroscopy. Compounds 1 and 2 were weakly cytotoxic in the A2780 human ovarian cell line, with IC (50) values of 6.8 and 8.0 microg/mL, respectively.

New cytotoxic triterpene acids from aboveground parts of Manihot esculenta from the Suriname rainforest.

Two novel triterpene acids, esculentoic acid A ( 1) and B ( 2) as well as the seven known compounds 3 - 9 were isolated from an EtOAc extract of leaves, stems, and twigs of Manihot esculenta by bioassay-guided fractionation for cytotoxic activity. The structures of the two new compounds were established as 3alpha-hydroxytaraxer-14-en-29-oic acid ( 1) and 3-oxotaraxer-14-en-29-oic acid ( 2) on the basis of 1D and 2D NMR spectroscopic data interpretation and chemical conversions. The two new compounds 1 and 2 showed moderate cytotoxicity against the A2780 human ovarian cancer cell line.

Bioactive saponins from Acacia tenuifolia from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Acacia tenuifolia using the engineered yeast strains 1138, 1140, 1353, and Sc7 as the bioassay tool resulted in the isolation of the three new saponins 3, 5, and 6 and the three known saponins 1, 2, and 4. The structures of the new compounds were established on the basis of HRMS, 1D and 2D NMR spectral data on the intact saponins, and GC-MS analyses of the sugars. Compounds 1,2 and 5,6 showed cytotoxicity against mammalian cell lines.

Isolation and absolute configuration of ent-Halimane diterpenoids from Hymenaea courbaril from the Suriname rain forest.

Bioactivity-directed fractionation of a methanol extract of Hymenaea courbaril afforded the three new diterpenoids (13R)-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (1), (2S,13R)-2,13-dihydroxy-1(10),14-ent-halimadien-18-oic acid (2), and (13R)-2-oxo-13-hydroxy-1(10),14-ent-halimadien-18-oic acid (3). The configurations of these compounds were determined from X-ray crystallography of 1, circular dichroism of 2 and 3, and spectral studies of prepared derivatives. Compound 1 exhibited weak cytotoxicity toward the 1138 mutant yeast strain and the A2780 human ovarian cancer cell line.