Evolutionary relevance of metabolite production in relation to marine sponge bacteria symbiont.

Sponges are habitats for a diverse community of microorganisms. Sponges provide shelter, whereas microbes provide a complementary defensive mechanism. Here, a symbiotic bacterium, identified as Bacillus spp., was isolated from a marine sponge following culture enrichment. Fermentation-assisted metabolomics using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) indicated that marine simulated nutrition and temperature was the optimum in metabolite production represented by the highest number of metabolites and the diverse chemical classes when compared to other culture media. Following large-scale culture in potato dextrose broth (PDB) and dereplication, compound M1 was isolated and identified as octadecyl-1-(2',6'-di-tert-butyl-1'-hydroxyphenyl) propionate. M1, at screening concentrations up to 10 mg/ml, showed no activity against prokaryotic bacteria including Staphylococcus aureus and Escherichia coli, while 1 mg/ml of M1 was sufficient to cause a significant killing effect on eukaryotic cells including Candida albicans, Candida auris, and Rhizopus delemar fungi and different mammalian cells. M1 exhibited MIC50 0.97 ± 0.006 and 7.667 ± 0.079 mg/ml against C. albicans and C. auris, respectively. Like fatty acid esters, we hypothesize that M1 is stored in a less harmful form and upon pathogenic attack is hydrolyzed to a more active form as a defensive metabolite. Subsequently, [3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid] (DTBPA), the hydrolysis product of M1, exhibited ~ 8-fold and 18-fold more antifungal activity than M1 against C. albicans and C. auris, respectively. These findings indicated the selectivity of that compound as a defensive metabolite towards the eukaryotic cells particularly the fungi, a major infectious agent to sponges. Metabolomic-assisted fermentation can provide a significant understanding of a triple marine-evolved interaction. KEY POINTS: • Bacillus species, closely related to uncultured Bacillus, is isolated from Gulf marine sponge • Metabolomic-assisted fermentations showed diverse metabolites • An ester with a killing effect against eukaryotes but not prokaryotes is isolated.

Flavonoids are promising safe therapy against COVID-19.

Flavonoids are a class of phenolic natural products, well-identified in traditional and modern medicines in the treatment of several diseases including viral infection. Flavonoids showed potential inhibitory activity against coronaviruses including the current pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and designated as COVID-19. Here, we have collected all data related to the potential inhibitory mechanisms of flavonoids against SARS-CoV-2 infection and their significant immunomodulatory activities. The data were mapped and compared to elect major flavonoids with a promising role in the current pandemic. Further, we have linked the global existence of flavonoids in medicinal plants and their role in protection against COVID-19. Computational analysis predicted that flavonoids can exhibit potential inhibitory activity against SARS-CoV-2 by binding to essential viral targets required in virus entry and/ or replication. Flavonoids also showed excellent immunomodulatory and anti-inflammatory activities including the inhibition of various inflammatory cytokines. Further, flavonoids showed significant ability to reduce the exacerbation of COVID-19 in the case of obesity via promoting lipids metabolism. Moreover, flavonoids exhibit a high safety profile, suitable bioavailability, and no significant adverse effects. For instance, plants rich in flavonoids are globally distributed and can offer great protection from COVID-19. The data described in this study strongly highlighted that flavonoids particularly quercetin and luteolin can exhibit promising multi-target activity against SARS-CoV-2, which promote their use in the current and expected future outbreaks. Therefore, a regimen of flavonoid-rich plants can be recommended to supplement a sufficient amount of flavonoids for the protection and treatment from SARS-CoV-2 infection.

Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis.

Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Herein, we have developed a series of compounds (UOSC-1-14) to selectively target Rhizopus melanin and explored this mechanism therapeutically. The compounds were designed based on the scaffold of the natural product, cuminaldehyde, identified from plant sources and has been shown to develop non-selective inhibition of melanin production. While all synthesized compounds showed significant inhibition of Rhizopus melanin production and limited toxicity to mammalian cells, only four compounds (UOSC-1, 2, 13, and 14) were selected as promising candidates based on their selective inhibition to fungal melanin. The activity of compound UOSC-2 was comparable to the positive control kojic acid. The selected candidates showed significant inhibition of Rhizopus melanin but not human melanin by targeting the fungal tyrosinase, and with an IC50 that are 9 times lower than the reference standard, kojic acid. Furthermore, the produced white spores were phagocytized easily and cleared faster from the lungs of infected immunocompetent mice and from the human macrophages when compared with wild-type spores. Collectively, the results suggested that the newly designed derivatives, particularly UOSC-2 can serve as promising candidate to overcome persistence mechanisms of fungal melanin production and hence make them accessible to host defenses.

Potential targeting of Hep3B liver cancer cells by lupeol isolated from Avicennia marina.

Medicinal plants are valuable sources of different active constituents that are known to have important pharmacological activities including anticancer effects. Lupeol, a pentacyclic triterpenoid, present in many medicinal plants, has a wide range of biological activities. Although the anticancer activity of lupeol was reported, the published data are inconsistent and the clear mechanism of action has never been assigned. The current study aims at investigating the anticancer specificity and mechanism of lupeol isolated from Avicennia marina, which grows in the desert of the United Arab Emirates. The compound was purified by chromatography and identified by spectroscopy. Compared with a negative control, lupeol caused significant (p < .001) growth inhibitory activity on MCF-7 and Hep3B parental and resistant cells by 45%, 46%, 72%, and 35%, respectively. The mechanism of action of lupeol was further explored by measuring its effect on key players in cancer development and progression, BCL-2 anti-apoptotic and BAX pro-apoptotic proteins. Lupeol significantly (p < .01) downregulated BCL-2 gene expression in parental and resistant Hep3B cells by 33 and 3.5 times, respectively, contributing to the induction of apoptosis in Hep3B cells, whereas it caused no effect on BAX. Furthermore, the immunoblotting analysis revealed that lupeol cleaved the executioner caspase-3 into its active form. Interestingly, lupeol showed no significant effect on the proliferation of monocytes, whereas it caused an increase in the sub-G1 population and a reduction in the apoptosis rates of monocytes at 48 and 72 h, indicative of no immuno-inflammatory responses. Collectively, lupeol can be considered as promising effective and safe anticancer agent, particularly against Hep3B cancer cells.

New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents.

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a-l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a-l). The novel series showed selective sub-micromolar IC50 growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC50 values of 0.31-0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC50 value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.

Essential Oil-Based Design and Development of Novel Anti-Candida Azoles Formulation.

Candida is the most common fungal class, causing both superficial and invasive diseases in humans. Although Candida albicans is the most common cause of fungal infections in humans, C. auris is a new emergent serious pathogen causing complications similar to those of C. albicans. Both C. albicans and C. auris are associated with high mortality rates, mainly because of their multidrug-resistance patterns against most available antifungal drugs. Although several compounds were designed against C. albicans, very few or none were tested on C. auris. Therefore, it is urgent to develop novel effective antifungal drugs that can accommodate not only C. albicans, but also other Candida spp., particularly newly emergent one, including C. auris. Inspired by the significant broad-spectrum antifungal activities of the essential oil cuminaldehyde and the reported wide incorporation of azoles in the antifungal drugs, a series of compounds (UoST1-11) was designed and developed. The new compounds were designed to overcome the toxicity of the aldehyde group of cuminaldehyde and benefit from the antifungal selectivity of azoles. The new developed UoST compounds showed significant anti-Candida activities against both Candida species. The best candidate compound, UoST5, was further formulated into polymeric nanoparticles (NPs). The new formula, UoST5-NPs, showed similar activities to the nanoparticles-free drug, while providing only 25% release after 24 h, maintainng prolonged activity up to 48 h and affording no toxicity. In conclusion, new azole formulations with significantly enhanced activities against C. albicans and C. auris, while maintaining prolonged action and no toxicities at lower concentrations, were developed.

SARS-CoV-2-free residual proteins mediated phenotypic and metabolic changes in peripheral blood monocytic-derived macrophages in support of viral pathogenesis.

The large-scale dissemination of coronavirus disease-2019 (COVID-19) and its serious complications have pledged the scientific research communities to uncover the pathogenesis mechanisms of its etiologic agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods of unveiling such mechanisms are rooted in understanding the viral agent's interactions with the immune system, including its ability to activate macrophages, due to their suggested role in prolonged inflammatory phases and adverse immune responses. The objective of this study is to test the effect of SARS-CoV-2-free proteins on the metabolic and immune responses of macrophages. We hypothesized that SARS-CoV-2 proteins shed during the infection cycle may dynamically induce metabolic and immunologic alterations with an inflammatory impact on the infected host cells. It is imperative to delineate such alterations in the context of macrophages to gain insight into the pathogenesis of these highly infectious viruses and their associated complications and thus, expedite the vaccine and drug therapy advent in combat of viral infections. Human monocyte-derived macrophages were treated with SARS-CoV-2-free proteins at different concentrations. The phenotypic and metabolic alterations in macrophages were investigated and the subsequent metabolic pathways were analyzed. The obtained results indicated that SARS-CoV-2-free proteins induced concentration-dependent alterations in the metabolic and phenotypic profiles of macrophages. Several metabolic pathways were enriched following treatment, including vitamin K, propanoate, and the Warburg effect. These results indicate significant adverse effects driven by residual viral proteins that may hence be considered determinants of viral pathogenesis. These findings provide important insight as to the impact of SARS-CoV-2-free residual proteins on the host cells and suggest a potential new method of management during the infection and prior to vaccination.

Efficient selective targeting of Candida CYP51 by oxadiazole derivatives designed from plant cuminaldehyde.

Candida infection represents a global threat with associated high resistance and mortality rate. Azoles such as the triazole drug fluconazole are the frontline therapy against invasive fungal infections; however, the emerging multidrug-resistant strains limit their use. Therefore, a series of novel azole UOSO1-15 derivatives were developed based on a modified natural scaffold to combat the evolved resistance mechanism and to provide improved safety and target selectivity. The antifungal screening against C. albicans and C. auris showed that UOSO10 and 12-14 compounds were the most potent derivatives. Among them, UOSO13 exhibited superior potent activity with MIC50 values of 0.5 and 0.8 µg mL-1 against C. albicans and C. auris compared to 25 and 600 µg mL-1 for fluconazole, respectively. UOSO13 displayed significant CaCYP51 enzyme inhibition activity in a concentration-dependent manner with an IC50 10-fold that of fluconazole, while exhibiting no activity against human CYP50 enzyme or toxicity to human cells. Furthermore, UOSO13 caused a significant reduction of Candida ergosterol content by 70.3% compared to a 35.6% reduction by fluconazole. Homology modeling, molecular docking, and molecular dynamics simulations of C. auris CYP51 enzyme indicated the stability and superiority of UOSO13. ADME prediction indicated that UOSO13 fulfils the drug-likeness criteria with good physicochemical properties.

Phenolic Contents and Antioxidant Activity of Citrullus colocynthis Fruits, Growing in the Hot Arid Desert of the UAE, Influenced by the Fruit Parts, Accessions, and Seasons of Fruit Collection.

Citrullus colocynthis (Cucurbitaceae) is an important medicinal plant traditionally used in the United Arab Emirates (UAE). In a recent study, it has been reported that different individuals of the same population of C. colocynthis, growing in the hot arid desert of the UAE, exhibited variations in their fruit size, color, and stripe pattern. In addition, these plants differed genetically, and their seeds showed variation in size, color, and germination behavior (hereinafter, these individuals are referred to as accessions). In the present study, the total phenolic content (TPC) and antioxidant activity of different fruit parts (rinds, pulps, and seeds) of three different accessions with significant genetic variations, from a single C. colocynthis population, were assessed in response to different seasonal environments. Green fruits were collected in summer and winter from three accessions growing in the botanic garden of the University of Sharjah, UAE. Methanolic extracts from different fruit parts were prepared. The TPC was qualitatively determined by a Folin-Ciocalteu assay, while the antioxidant capacity was analyzed using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging ability. The metabolic profiling of the antioxidant metabolites was determined using a gas chromatograph coupled to mass spectrometry (GC-MS), associated with a literature search. The results showed that the TPC and the DPPH free radical scavenging activity varied between seasons, accessions, and fruit parts. The highest phenolics were in rinds, but the highest antioxidant activities were in seeds during the summer, reflecting the role of these compounds in protecting the developed seeds from harsh environmental conditions. The metabolomic analysis revealed the presence of 28 metabolites with significant antioxidant activities relevant to fruit parts and season. Collectively, the formation of phenolics and antioxidant activity in different fruit parts is environmentally and genetically dependent.

Novel Secreted Peptides From Rhizopus arrhizus var. delemar With Immunomodulatory Effects That Enhance Fungal Pathogenesis.

Secreted fungal peptides are known to influence the interactions between the pathogen and host innate immunity. The aim of this study is to screen and evaluate secreted peptides from the fungus Rhizopus arrhizus var. delemar for their immunomodulatory activity. By using mass spectrometry and immuno-informatics analysis, we identified three secreted peptides CesT (S16), Colicin (S17), and Ca2+/calmodulin-dependent protein kinase/ligand (CAMK/CAMKL; S27). Culturing peripheral blood-derived monocytic macrophages (PBMMs) in the presence of S16 or S17 caused cell clumping, while culturing them with S27 resulted in the formation of spindle-shaped cells. S27-treated PBMMs showed cell cycle arrest at G0 phase and exhibited alternatively activated macrophage phenotype with pronounced reduction in scavenger receptors CD163 and CD206. Homology prediction indicated that IL-4/IL-13 is the immunomodulatory target of S27. Confirming this prediction, S27 initiated macrophage activation through phosphorylation of STAT-6; STAT-6 inhibition reversed the activity of S27 and reduced the formation of spindle-shaped PBMMs. Lastly, S27 treatment of PBMMs was associated with altered expression of key iron regulatory genes including hepcidin, ferroportin, transferrin receptor 1, and ferritin in a pattern consistent with increased cellular iron release; a condition known to enhance Rhizopus infection. Collectively, R. arrhizus var. delemar secretes peptides with immunomodulatory activities that support fungal pathogenesis. Targeting the IL-4/IL-13R/STAT-6 axis is a potential therapeutic approach to enhance the PBMM-mediated fungal phagocytosis. This represents a potential new approach to overcome lethal mucormycosis.

The Anti-Candida Activity of Tephrosia apollinea Is More Superiorly Attributed to a Novel Steroidal Compound with Selective Targeting.

Tephrosia is widely distributed throughout tropical, subtropical, and arid regions. This genus is known for several biological activities, including its anti-Candida activity, which is mainly attributed to prenylated flavonoids. The biological activities of most Tephrosia species have been studied, except T. apollinea. This study was conducted to investigate the underlying anti-Candida activity of T. apollinea, wildly grown in the United Arab Emirates (UAE). The T. apollinea plant was collected, dried, and the leaves were separated. The leaves were ground and extracted. The dried extract was subjected to successive chromatography to identify unique phytochemicals with a special pharmacological activity. The activity of the compound was validated by homology modeling and molecular docking studies. A novel steroidal compound (ergosta-6, 8(14), 22, 24(28)-tetraen-3-one) was isolated and named TNS. In silico target identification of TNS revealed a high structural similarity with the Candida 14-α-demethylase enzyme substrate. The compound exhibited a significant anti-Candida activity, specifically against the multi-drug-resistant Candida auris at MIC50, 16 times less than the previously reported prenylated flavonoids and 5 times less than the methanol extract of the plant. These findings were supported by homology modeling and molecular docking studies. TNS may represent a new class of Candida 14-α-demethylase inhibitors.

Marine Sponge is a Promising Natural Source of Anti-SARS-CoV-2 Scaffold.

The current pandemic caused by SARS-CoV2 and named COVID-19 urgent the need for novel lead antiviral drugs. Recently, United States Food and Drug Administration (FDA) approved the use of remdesivir as anti-SARS-CoV-2. Remdesivir is a natural product-inspired nucleoside analogue with significant broad-spectrum antiviral activity. Nucleosides analogues from marine sponge including spongouridine and spongothymidine have been used as lead for the evolutionary synthesis of various antiviral drugs such as vidarabine and cytarabine. Furthermore, the marine sponge is a rich source of compounds with unique activities. Marine sponge produces classes of compounds that can inhibit the viral cysteine protease (Mpro) such as esculetin and ilimaquinone and human serine protease (TMPRSS2) such as pseudotheonamide C and D and aeruginosin 98B. Additionally, sponge-derived compounds such as dihydrogracilin A and avarol showed immunomodulatory activity that can target the cytokines storm. Here, we reviewed the potential use of sponge-derived compounds as promising therapeutics against SARS-CoV-2. Despite the reported antiviral activity of isolated marine metabolites, structural modifications showed the importance in targeting and efficacy. On that basis, we are proposing a novel structure with bifunctional scaffolds and dual pharmacophores that can be superiorly employed in SARS-CoV-2 infection.

Avicennia marina a natural reservoir of phytopharmaceuticals: Curative power and platform of medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Avicennia marina (Forssk.) Vierh. is a historic plant, well-known for many centuries in traditional and folk use medicine. A. marina is an evergreen tree belongs to Acanthaceae family. The plant is the most widespread mangrove in the tropical and subtropical regions of Indo-West-Pacific area. Current scientific data confirmed the medicinal values of A. marina. The pharmacological activity of the plant is attributed to the presence of several phytochemical classes. AIM OF THE STUDY: To evaluate the link between the traditional use of the plant and the scientific data accumulated over time including both the phytochemical analysis and therapeutic activities. Additionally, to evaluate the usage of obtained data for further development of the plant and its products in the pharmaceutical market. MATERIALS AND METHODS: The data related to traditional medicine, therapeutic uses, phytochemical analysis and market availability of A. marina and its products from different geographical regions were collected. The collected data was compared and the research gaps were identified in order to highlight areas that can be employed to improve plant-based research and development. RESULTS: Although the wide geographical distribution of the plant, its historic traditional use, richness of phytochemicals and diverse pharmacological activities, the utilization of these data has never been exploited for human health and several gaps were identified. These gaps include the lack of phyto-geographical comparison of the plant, the lack of proper mapping of traditional use to the scientific data and inadequate exploration of plant phytochemicals by researchers. CONCLUSIONS: A. marina is an old tree that has evolved over centuries and adapted diverse climates. It contains a pool of potential phytochemicals that can be employed for the discovery of drugs after careful studies. Scientists are required to invest money and time to explore these renewable and natural sources of drugs and design drug formulations to overcome current difficult to treat health issues and fight against the era of drug resistant.

Design and synthesis of new drugs inhibitors of Candida albicans hyphae and biofilm formation by upregulating the expression of TUP1 transcription repressor gene.

Candida albicans is a common human fungal pathogen that causes disease ranging from superficial to lethal infections. C. albicans grows as budding yeast which can transform into hyphae in response to various environmental or biological stimuli. Although both forms have been associated with virulence, the hyphae form is responsible for the formation of multi-drug resistance biofilm. Here, new compounds were designed to selectively inhibit C. albicans hyphae formation without affecting human cells to afford sufficient safety. The newly designed 5-[3-substitued-4-(4-substituedbenzyloxy)-benzylidene]-2-thioxo-thiazolidin-4-one derivatives, named SR, showed very specific and effective inhibition activity against C. albicans hyphae formation. SR compounds caused hyphae inhibition activity at concentrations 10-40 fold lower than the concentration required to inhibit Candida yeast and bacterial growths. The anti-hyphae inhibition activities of SR compounds were via activation of the hyphae transcription repressor gene, TUP1. Correlation studies between the expression of TUP1 gene and the activity of SR compounds confirmed that the anti-C. albicans activities of SR compounds were via inhibition of hyphae formation. The newly designed SR compounds showed 10-40% haemolytic activity on human erythrocytes when compared to 100% haemolysis by 0.1% triton employed as positive control. Furthermore, theoretical prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of SR compounds confirmed their safety, efficient metabolism and possible oral bioavailability. With the minimal toxicity and significant activity of the newly-designed SR compounds, a future optimization of pharmaceutical formulation may develop a promising inhibitor of hyphal formation not only for C. albicans but also for other TUP1- dependent dimorphic fungal infections.

Novel betulin derivative is responsible for the anticancer folk use of Ziziphus spina-christi from the hot environmental habitat of UAE.

ETHNOPHARMACOLOGICAL RELEVANCE: Several natural products derived from plant sources are developed to remarkable medicines based on their traditional uses. Ziziphus, a worldwide known plant, is proven for potential cytotoxic activity. However, the plant growing at the unique hot environmental climate of UAE was never investigated. Different phytochemicals may be produced from the same plant genotype at different climates leading to variable pharmacological activities. AIM OF THE STUDY: The study was conducted in order to investigate phytochemicals in the UAE native Z. spina-christi plant and its anticancer activity. MATERIALS AND METHODS: Z. spina-christi plant were collected, dried and dissected into leaves, stems and thorns. The plant organs were subjected to comparative fractionation-based anticancer assay followed by spectroscopic analysis of a uniquely isolated compound. RESULTS: The results indicate that a novel betulin derivative (13-dehydrobetulin) isolated from plant stem exhibited substantial anticancer activity specifically against liver cancer and with wide therapeutic range. CONCLUSIONS: Growth of cytotoxic traditionally-known plant remedy at harsh environmental habitat advances its anticancer activity due to production of novel phytochemical with optimum activity and minimal toxicity. Furthermore, such approach may be a future to develop novel lead compounds with optimum activity.

Lipophilic Metabolites and Anatomical Acclimatization of Cleome amblyocarpa in the Drought and Extra-Water Areas of the Arid Desert of UAE.

Plants adapt to different environmental conditions by developing structural and metabolic mechanisms. In this study, anatomical features and lipophilic metabolites were investigated in Cleome amblyocarpa Barr. & Murb., Cleomaceae plants growing in the arid desert of United Arab Emirates (UAE) in either low-water or extra-water areas, which were caused by the surrounding road run-off. The plant showed the presence of shaggy-like trichomes. The plant also developed special mechanisms to ensure its survival via release of lipophilic metabolites. The lipophilic metabolites, stained red with Sudan III, were apparently released by glandular trichomes and idioblasts of the shoot and roots, respectively. The identified lipophilic metabolites included those required for drought tolerance, protection against pathogens invasion, and detoxification. Plants growing in the low-water area caused an increase in the production of lipophilic metabolites-in particular, hydrocarbons and terpenoids. The lipophilic metabolites are known to provide the plant with unique waxy surfaces that reduce water loss and avoid penetration by pathogens. The release of lipid metabolites and the presence of shaggy-like trichomes represented unique features of the species that have never been reported. The provided chemical ecology information can be extended for several plant-related applications, particularly including drought tolerance.