In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.

Genus Salsola (family Amaranthaceae) is one of the most prevailing genera in Saudi Arabia. Although several species were reported for their traditional uses, the majority of Salsola species still need to be phytochemically and biologically explored. The current study presents the GC-MS profiling as well as an in vitro investigation of the bioactivities of the n-hexane extracts from the five Salsola species: Salsola arabica, S. cyclophylla, S. imbricata, S. incanescens and S. villosa. Additionally, the compounds identified in the most active extracts were screened for their interaction with the active sites of cyclooxygenase enzyme isoforms (COX-1 and COX-2). GC-MS analysis of the n-hexane extracts from the five species resulted in the identification of 67 constituents. Oleic acid (75.57%), 1-octadecene (14.46%), cinnamaldehyde α-hexyl (57.15%), octacosyl heptafluorobutyrate (25.36%) and hexadecanoic acid methyl ester (26.15%) represent the major constituents in S. arabica, S. cyclophylla, S. imbricata, S. inscanescence and S. villosa, respectively. Results of bioactivity testing highlighted S. villosa as having the highest anti-oxidant activity (IC₅₀ 0.99 ± 0.05 mg/mL), which was closely followed by S. cyclophylla (IC₅₀ 1.36 ± 0.06 mg/mL) compared to the IC₅₀ of 0.16 ± 0.01 mg/mL recorded by ascorbic acid. S. villosa was further noted for having the strongest COX-2 inhibitory activity (IC₅₀ 4.6 ± 0.13 µg/mL) among the tested extracts followed by S. arabica (IC₅₀ 13.1 ± 0.37 µg/mL) and S. cyclophylla (IC₅₀ 20.1 ± 0.57 µg/mL). On the other hand, S. imbricata extract displayed the most characteristic inhibition activity against COX-1 (IC₅₀ 10.2 ± 0.52 µg/mL), which was non-significant from the standard drug celecoxib. Based upon bioactivity results, the phytoconstituents identified in S. villosa and S. imbricata extracts were investigated for their capability to interact with the active sites of both cyclooxygenase enzyme isoforms adopting molecular docking. Results indicated the possibility to incorporate the compounds to active sites of the enzymes where some of them bind with their polar end into the cavity beyond Arg120 and their aliphatic chain oriented to the catalytically important Tyr385 similar to the natural substrate arachidonic acid, indicating that they could be promising candidates for the future development of selective COX inhibitors.

Euphorbia is a large genus of flowering plants with a great diversity in metabolic pattern. Testing the cytotoxic potential of fifteen Euphorbia species revealed highest activity of E. officinarum L. against human colon adenocarcinoma (CACO2) cell line (IC₅₀ 7.2 µM) and of E. lactea Haw. against human hepatoma (HepG2) and human breast adenocarcinoma (MCF-7) cell lines (IC₅₀ 5.2 and 5.1 µM, respectively). Additionally, metabolic profiling of the fifteen tested species, using LC-HRMS, for dereplication purposes, led to the annotation of 44 natural compounds. Among the annotated compounds, diterpenoids represent the major class. Dereplication approach and multivariate data analysis are adopted in order to annotate the compounds responsible for the detected cytotoxic activity. Results of Principle component analysis (PCA) come in a great accordance with results of biological testing, which emphasized the cytotoxic properties of E. lactea Haw. A similarity correlation network showed that the two compounds with the molecular formula C₁₆H₁₈O₈ and C₂₀H₃₀O₁₀, are responsible for cytotoxic activity against MCF-7 and HepG2 cell lines. Similarly, the compound with molecular formula C₁₈H₃₅NO correlates with cytotoxic activity against CACO2.

Halophytes are salt tolerating plants that grow in variable habitats, such as deserts and steppes. Chenopodiaceae and Amaranthaceae are two families widely prevailing in Saudi Arabia. They include plenty of previously unexplored halophytes. In a research program aimed at exploring the phytochemical content and biological potential of Qassim region halophytes; the current study presents phytochemical analysis as well as assessment of the antioxidant and antimicrobial activity of the five halophytes: Agathophora alopecuroides var. papillosa, Atriplex leucoclada, Halothamnus bottae, Salsola villosa, and Salicornia persia ssp. Iranica. Results of qualitative phytochemical analysis indicated the presence of saponins, tannins, sterols, carbohydrates, and flavonoids in all tested species. The comparison of the phenolic content of the five species revealed the highest total phenolics content and total flavonoids content in S. villosa (135.2 mg GAE/g and 18.2 mg QE/g, respectively) and A. leucoclada (134.1 mg GAE/g and 21.2 mg QE/g, respectively). Investigation of the antioxidant potential demonstrated the highest activity of H. bottae followed by S. villosa (IC₅₀ 263.7 and 290.7 μg/mL, respectively). Additionally, screening of the antimicrobial activity revealed potent activity of Salicornia persia, H. bottae, and S. villosa against Staphylococcus aureus while none of the tested extracts displayed antifungal activity against tested fungal species.

Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Moreover, the severe side effects and the reported drug resistance make it an urgent need to search for effective drugs that can replace or supplement those currently used. In a research program designed to investigate the antileishmanial activity of plants collected from the Egyptian flora, twenty extracts from fifteen plants growing in Egypt have been investigated for in vitro leishmanicidal activity against Leishmania donovani promastigotes. Among the tested extracts, the methanol extract of Euphorbia peplus aerial parts exhibited a significant antileishmanial activity as it produced 100% inhibition of growth with activity similar to amphotericin B. The total extract was subjected to liquid-liquid fractionation using solvents of different polarities, followed by testing the antileishmanial activity of the successive fractions. Phytochemical exploration of the active n-hexane fraction (which produced 75% inhibition of growth) led to isolation of four compounds: simiarenol (1), 1-hexacosanol (2), β-sitosterol (3), and β-sitosterol-3-O-glucoside (4) from the biologically active sub-fractions. Structure elucidation was aided by 1D and 2D NMR techniques. In conclusion, E. peplus plant has many non-polar secondary metabolites that can be used as drug leads for treatment of leishmaniasis.

Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant native to different tropical regions. Although some reports addressed their anti-inflammatory, cytotoxic, and antituberculotic effects, their hepatoprotective potential is yet to be discovered. Accordingly, this study investigated the crude extract and different fractions of the plant leaves; metabolic profiling using liquid chromatography/high-resolution electrospray ionization mass spectroscopy (LC–HRESIMS) analysis, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties for the dereplicated metabolite via online PreADMET program, ROS scavenger activity on the Hep G2 human liver cancer cell line, and the possible hepatic cellular treatment effects in alcohol-inflamed liver female Wistar albino rats. Metabolic profiling dereplicated a total of 28 metabolites from the crude extract and its various fractions. In silico ADMET and ROS scavenger activity screening suggested plant metabolites are of potential bioactivity. In vivo hepatic treatment with crude, defatted crude, and n-hexane leave extracts suggested all extracts significantly improved liver damage, which was indicated by the reduction of elevated serum levels of bilirubin, AST, ALT, ALP, CRP, TNF-α, ICAM-1, VCAM-1, and MDA. The reduced levels of GSH and TAC were normalized during the study. Histological examinations of liver tissue showed collagen fiber distribution nearly back to its normal pattern. The anti-inflammatory and antioxidant potentials of Premna odorata extracts could be partly related to the combined effects of these phytochemicals or their synergistic interactions.