Three new caryophyllane-type sesquiterpenoids, linariophyllenes A−C (1−3), two new hamamelitol derivatives, linaritols A (4) and B (5), two new chromones, linariosides A (6) and B (7), and three known chromones, cnidimol C (8), monnieriside A (9), and undulatoside A (10), were identified from the aerial parts of Evolvulus linarioides. The structures of these compounds were elucidated by NMR, MS, and IR data. The absolute configurations of compounds 1−5 and 7 were established via electronic circular dichroism data. The anti-inflammatory potential of compounds 1−5 and 7−10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and proinflammatory cytokine IL-1β by stimulated J774 macrophages. Compounds tested at noncytotoxic concentrations inhibited NO production by macrophages, exhibiting IC 50 values between 17.8 and 66.2 μM, and inhibited IL-1β production by stimulated macrophages by 72.7−96.2%.

This study represents the first phytochemical analysis of Stillingia loranthacea (S. loranthacea) and describes new terpenoids obtained from the root bark of this species. The fractionation of the hexane extract from the root bark led to the isolation of two new 28-nor-taraxarenes derivatives, loranthones A and B (1 and 2), four new tigliane diterpenes (5−8), three known tigliane diterpenes (9−11), and three known flexibilene diterpenes, tonantzitlolones A−C (12−14). The investigation of these compounds and the use of a molecular networking-based prioritization approach afforded two other new 28-nor-taraxarenes, loranthones C and D (3 and 4). The cytotoxicity of compounds 1, 2, and 5−14 was evaluated against Vero cells, and their 20% cytotoxic concentration (CC 20 ) values varied from 8.7 to 328 μM; antiviral activity was tested against an epidemic Zika virus (ZIKV) strain circulating in Brazil. Six out of 12 compounds (2, 5, 9−11, and 14) exhibited significant antiviral effects against ZIKV. Specifically, compounds 2 and 5 offered the most promise as lead compounds as they had a 1.7 and 1.8 log 10 TCID 50 /mL reduction in ZIKV replication, respectively. Together, the present findings have identified S. loranthacea terpenoids as potent anti-ZIKV inhibitors and pave the way to the development of possible new treatments against this devastating pathogen.

Lamiaceae is one of the largest families of angiosperms and is classified into 12 subfamilies that are composed of 295 genera and 7775 species. It presents a variety of secondary metabolites such as diterpenes that are commonly found in their species, and some of them are known to be chemotaxonomic markers. The aim of this work was to construct a database of diterpenes and to use it to perform a chemotaxonomic analysis among the subfamilies of Lamiaceae, using molecular descriptors and self-organizing maps (SOMs). The 4115 different diterpenes corresponding to 6386 botanical occurrences, which are distributed in eight subfamilies, 66 genera, 639 different species and 4880 geographical locations, were added to SistematX. Molecular descriptors of diterpenes and their respective botanical occurrences were used to generate the SOMs. In all obtained maps, a match rate higher than 80% was observed, demonstrating a separation of the Lamiaceae subfamilies, corroborating with the morphological and molecular data proposed by Li et al. Therefore, through this chemotaxonomic study, we can predict the localization of a diterpene in a subfamily and assist in the search for secondary metabolites with specific structural characteristics, such as compounds with potential biological activity.

Introduction: Given the diversity of secondary metabolites produced by species of the genus Erythroxylum, in addition to the many methods that have already been described in the literature, modern screening and identification methodologies, such as dereplication, represent an efficient and quick strategy compared to the classic techniques linked to natural product research. Objective: The objective of the present study was to determine the phenolic profiles obtained from three species of Erythroxylum (Erythroxylum pauferrense Plowman, Erythroxylum pulchrum A.St.-Hil. and Erythroxylum simonis Plowman) by dereplication using liquid chromatography coupled with ESI-MS n and HRESIMS. Material and Methods: Ethyl acetate and n-butanolic fractions from crude ethanolic extract of Erythroxylum species were analyzed by HPLC-ESI-MS n and HPLC-HRESIMS, in order to identify its corresponding compounds. Experiments were performed in negative ionization mode, and the metabolites were provisionally identified based on deprotonated molecules, molecular formulas, fragmentation patterns and literature data. The corresponding isolated compounds were characterized by 1 H and 13 C NMR spectroscopy.Results: According to the dereplication method, it was possible to establish and compare the phenolic profile of the corresponding species by the assignment of 55 compounds, most of which were first described in these species and among which some were also new to the Erytroxylum genus. Additionally, nine compounds were isolated, including biphenyl-3,3 0 ,4,4 0 -tetraol, where the mass spectral data were not sufficient for their identification, and reported for the first time in the Erythroxylaceae family. Conclusion: This research contributes to the phytochemical knowledge of theErythroxylum genus and demonstrates the importance of the dereplication method regarding the investigation of natural products, enabling accurate identification of the metabolites while avoiding the efforts and material expenses involved in the isolation of known compounds.

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