Ursolic acid inhibits NF-κB signaling and attenuates MMP-9/TIMP-1 in progressive osteoarthritis: a network pharmacology-based analysis.

Osteoarthritis (OA) is a degenerative joint disease, characterized by infiltration of monocytes into the synovial joint which promotes inflammation, stiffness, joint swelling, cartilage degradation and further bone destruction. The leaves of Ocimum forskolei have been used for inflammation-related disease management in traditional medicine. Additionally, the downregulation of NF-κB and the MMP/TIMP-1 ratio has been shown to protect against OA. The LC-HR-MS metabolic analysis of Ocimum yielded 19 putative compounds, among which ursolic acid (UA) was detected. Ursolic acid possesses significant anti-inflammatory effects and has been reported to downregulate oxidative stress and inflammatory biomarkers. It was tested on rats in a model of intra-articular carrageenan injection to investigate its efficacy on osteoarthritis progression. The UA emulgel exerted chondroprotective, analgesic and local anaesthetic efficacies confirmed via histopathological investigation and radiographical imaging. A network pharmacology followed by molecular docking highlighted TNF-α, TGF-ß and NF-κB as the top filtered genes. Quantitative real-time PCR analysis showed that UA significantly attenuated serum levels of TNF-α, IL-1ß, NF-κB, MMP-9/TIMP-1 and elevated levels of TGF-ß. Taken together, these results suggest that UA could serve as a functional food-derived phytochemical with a multi-targeted efficacy on progression of OA, regulating the immune and inflammatory responses, particularly, attenuating chondrocytes degeneration via suppression of NF-κB and MMP-9/TIMP-1. Accordingly, UA might be a promising alternative to conventional therapy for safe, easily applicable and effective management of OA.

Isolation and structural characterization of phytoconstituents from leaves of Bignonia binata.

Phytochemical investigation of Bignonia binata leaves led to the isolation of three new compounds: including a glycoside of simple alcohol, namely binatoside (2), 3,4-dihydroxy-N-methyl piperidin-2-one (7), and a phenyl ethanoid glycoside, namely bignanoside C (8), alongside with five known compounds; including a glycoside of simple alcohol; (2S) propane-1,2-diol 1-O-(6-O-caffeoy1)-ß-D-glucopyranoside (1), phenyl ethanoids; leucosceptoside A (3) and plantainoside C (4), and iridoids; ipolamiide (5) and strictoloside (6). The structure of the isolated compounds was elucidated by various spectroscopic methods, including 1 D and 2 D NMR experiments, HR-ESI-MS as well as by comparison with the literature.

Paralemnalia thyrsoides-associated fungi: phylogenetic diversity, cytotoxic potential, metabolomic profiling and docking analysis.

BACKGROUND: Cancer continues to be one of the biggest causes of death that affects human health. Chemical resistance is still a problem in conventional cancer treatments. Fortunately, numerous natural compounds originating from different microbes, including fungi, possess cytotoxic characteristics that are now well known. This study aims to investigate the anticancer prospects of five fungal strains that were cultivated and isolated from the Red Sea soft coral Paralemnalia thyrsoides. The in vitro cytotoxic potential of the ethyl acetate extracts of the different five isolates were evaluated using MTS assay against four cancer cell lines; A549, CT-26, MDA-MB-231, and U87. Metabolomics profiling of the different extracts using LC-HR-ESI-MS, besides molecular docking studies for the dereplicated compounds were performed to unveil the chemical profile and the cytotoxic mechanism of the soft coral associated fungi. RESULTS: The five isolated fungal strains were identified as Penicillium griseofulvum (RD1), Cladosporium sphaerospermum (RD2), Cladosporium liminiforme (RD3), Penicillium chrysogenum (RD4), and Epicoccum nigrum (RD5). The in vitro study showed that the ethyl acetate extract of RD4 exhibited the strongest cytotoxic potency against three cancer cell lines A549, CT-26 and MDA-MB-231 with IC50 values of 1.45 ± 8.54, 1.58 ± 6.55 and 1.39 ± 2.0 µg/mL, respectively, also, RD3 revealed selective cytotoxic potency against A549 with IC50 value of 6.99 ± 3.47 µg/mL. Docking study of 32 compounds dereplicated from the metabolomics profiling demonstrated a promising binding conformation with EGFR tyrosine kinase that resembled its co-crystallized ligand albeit with better binding energy score. CONCLUSION: Our results highlight the importance of soft coral-associated fungi as a promising source for anticancer metabolites for future drug discovery.

Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L'Her.) Herb. Bulbs.

Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3'-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3',4'-methylenedioxyflavan-3-ol (11), 7-hydroxy-3',4'-methylenedioxy flavan (12), 2',4'-dihydroxy-3'-methyl-3,4-methylenedioxychalcone (13), and isoliquiritigenin (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), and 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) and narciprimine (15)], one phenol derivative [p-nitrophenol (5)], and one steroid [ß-sitosterol 3-O-ß-glucopyranoside (16)]. Their structures were elucidated by combining one- and two-dimensional NMR and ESI-MS techniques and by comparison with the reported literature data and some authentic samples. Except for lycorine (1), the isolated metabolites were obtained herein for the first time from Hippeastrum plants, among which compound 13 was identified as a new chalcone derivative. Additionally, the total phenolic and flavonoid contents of the total ethanol extract and different fractions of the bulbs were determined by the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential was compared using the phosphomolybdenum and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, the binding affinities of compounds 1-16 to some key target proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), were screened and compared using molecular docking analysis. The possible chemotaxonomic significance of the identified metabolites was also discussed.

Metabolic profiling and biological potential of the marine sponge associated Nocardiopsis sp. UR67 along with docking studies.

This work was performed to dig into the phytochemical composition and bioactivities of Nocardiopsis sp. UR67 associated with the marine sponge Callyspongia sp. It was fermented in suspension and immobilised in calcium alginate bead cultures. The ethyl acetate extracts, afforded from the broth in each case named EG-49 and J-48g, respectively, revealed 16 chemical principles mostly belonging to polyketides, macrolides, and peptides. EG-49 and J-48g displayed anti-Candida albicans activity with IC50 values of 8.1 and 8.3 µg/mL, and a substantial cytotoxic effect against lung adenocarcinoma H1650 at IC50 12.6 and 13.7 µg/mL, respectively. However, only EG-49 exhibited a noteworthy anti-trypanosomal activity at 7.5 µg/mL. Molecular docking of the characterised compounds against Trypanosoma brucei trypanothione reductase demonstrated the highest binding models of griseochelin-methyl ester (9) and filipin-II (11), which drew considerable significance of the metabolites derived from Nocardiopsis sp. UR67 developing potential T. brucei trypanothione reductase inhibitors.

Aureanin: a new iridoid from the leaves of Tabebuia aurea (Silva Manso) Benth. & Hook.f. ex S.Moore.

One new iridoid named aureanin (1) was isolated from the leaves of Tabebuia aurea (Silva Manso) Benth. & Hook.f. ex S.Moore, together with eight known compounds, isoquercetin (2), astragalin (3), callicoside B (4), amphipaniculoside E (5), rehmaglutin D (6), quercetin-3-sambubioside (7), rutin (8), kaempferol-3-O-rutinoside (9). The structures of the isolated compounds were elucidated and confirmed by spectroscopic methods, including 1 D and 2 D NMR experiments, as well as HR-ESI-MS. Compounds 1-9 were evaluated for their in vitro cytotoxic activity against three human cancer cell lines (A549, HepG2, and MCF-7) and Leishmania major. Compound 4 showed activity against A549 (IC50: 36.8 ± 1.5 µg/mL, etoposide (positive control): 28.1 ± 4.2 µg/mL), however, none of the compounds were active against L. major.

Cytotoxic and antileishmanial triterpenes of Tabebuia aurea (Silva Manso) leaves.

The bioactivity-guided fractionation of the total ethanolic extract of the leaves of Tabebuia aurea revealed the cytotoxic and antileishmanial potency of the ethyl acetate fraction, in which its phytochemical investigation resulted in the isolation of five triterpenes; identified as oleanolic acid (1), ursolic acid (2), pomolic acid (3), tormentic acid (4), 3ß,6ß,19α-trihydroxy-urs-12-en-28-oic acid (5) in addition to one triterpenoid glucoside, spathodic acid 28-O-ß-D-glucopyranoside (6). Whereas compound 1 showed cytotoxic activity against three different cell lines; A549, MCF-7 and HepG2 with IC50 values of 31.7 ± 1.2, 27.4 ± 1.8 and 28.8 ± 1.1 µg/mL, respectively (etoposide as a positive control: 28.1 ± 4.2, 22.5 ± 4.5, and 20.4 ± 0.8 µg/mL, respectively), while compounds 1 and 2 showed antileishmanial activity with IC50 values of 10.2 ± 0.9 µg/mL and 5.1 ± 0.4 µg/mL, respectively (miltefosine: 7.7 ± 2.1 µg/mL).

Cytotoxic potential of Nephthea sp.-derived actinomycetes supported by metabolomics analysis.

Soft corals and associated microorganisms are known to produce leads for anticancer drugs. Keeping this in mind, Nephthea sp.; a Red Sea soft coral was investigated for the first time using the OSMAC approach. Two isolates, Streptomyces sp. UR63 and Micrococcus sp. UR67 were identified. Their extracts revealed the presence of alkaloids, macrolides, quinones, fatty acids and terpenoids. Further comparison through a set of multivariate data analyses revealed their unique chemical profiles. The extracts displayed inhibitory potencies against HepG-2, Caco-2 and MCF-7 tumor cell lines with IC50 values ranging from 11.4 to 38.7 µg/mL when compared with the positive control, doxorubicin. The study not only highlights the cytotoxic potential of soft coral-associated actinomycetes but also shows the advantage of using the OSMAC approach in this regard.

Cytotoxicity and chemical profiling of the Red Sea soft corals Litophyton arboreum.

The objective of this research was to evaluate the cytotoxic activities of the fractions and isolated compounds of the soft corals Litophyton arboreum against A549, MCF-7 and HepG2 cell lines by MTT assay method, and to chemically investigate the various metabolites of its total extract using LC-HR-ESI-MS metabolomic profiling. The metabolomic profiling revealed the presence of various metabolites, mainly sesquiterpenes and steroids reported for the first time in L. arboreum. Additionally, eight compounds (1-8) have been isolated from the n-hexane-chloroform (1:1) fraction that exhibited noticeable activity towards A549, MCF-7 and HepG2 cell lines. The steroids (5 and 6), and the sesquiterpene (1) exerted noticeable activity against A549 cell line (IC50 28.5 ± 4.4, 36.9 ± 2.9 and 67.3 ± 9.9 µM/mL, respectively) compared to etoposide as standard cytotoxic agent (IC50 48.3 ± 7.6 µM/mL). Compound 6 also exhibited cytotoxicity against MCF-7 cell line (IC50 55.3 ± 4.9 µM/mL).

Cytotoxic activity of actinomycetes Nocardia sp. and Nocardiopsis sp. associated with marine sponge Amphimedon sp.

Cancer is a hazard life-threatening disease, which affect huge population worldwide. Marine actinomycetes are considered as promising source for potential chemotherapeutic agents. In our study, we carried out metabolic profiling for Nocardia sp. UR 86 and Nocardiopsis sp. UR 92 that were cultivated from the Red Sea sponge Amphimedon sp. to investigate their chemical diversity using different media conditions. The crude culture extracts were subjected to high-resolution mass spectrometry (HRMS) analysis. The chemical profiles of the different extracts of Nocardia sp. UR 86 and Nocardiopsis sp. UR 92 revealed their richness in diverse metabolites and consequently twenty compounds (1-20) were annotated. Moreover, the obtained extracts of the differently cultivated Nocardia sp. UR 86 and Nocardiopsis sp. UR 92 were investigated against three cell lines HepG2, MCF-7 and CACO2 and revealed the targeted cytotoxicity of Nocardia sp. and Nocardiopsis sp. metabolites against the three cell lines.

Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation.

The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150 ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of -110 kJ/mol. This study sheds light on the structure-based design of natural flavonoids as anti-SARS-CoV-2 drugs targeting the nsp16/10 complex.Communicated by Ramaswamy H. Sarma.

LC-MS-based identification of bioactive compounds and hepatoprotective and nephroprotective activities of Bignonia binata leaves against carbon tetrachloride-induced injury in rats.

The chemical profiling of the main phytoconstituents of total ethanolic extract (TEE) and its different fractions of Bignonia binata leaves was dereplicated using liquid chromatography-high resolution-electrospray ionisation-mass spectrometry (LC-HR-ESI-MS), revealed the presence of various classes of secondary metabolites; eight phenylethanoids, two flavonoidal glycosides and two iridoids. Moreover, the hepatoprotective and nephroprotective activities of the TEE and its different fractions were investigated in carbon tetrachloride (CCl4)-intoxicated rats and were compared with those of silymarin-treated group, revealing the highest potency of the EtOAc group, followed by the aqueous one in improving the CCl4-induced alterations in several biochemical parameters. Besides, EtOAc and aqueous fractions exhibited the most inhibition of CCl4-induced inflammatory mediators and improving the changes in the histopathological structures of the liver and kidney. In addition, the EtOAc fraction demonstrated the highest total phenolic content, whereas TEE showed the highest amount of total flavonoid content.[Formula: see text].

Natural metabolites from the soft coral Nephthea sp. as potential SARS-CoV-2 main protease inhibitors.

The ongoing spread of SARS-CoV-2 has created a growing need to develop effective antiviral treatments; therefore, this work was undertaken to delve into the natural metabolites of the Red Sea soft coral Nephthea sp. (family Nephtheidae) as a source of potential anti-COVID-19 agents. Overall, a total of 14 structurally diverse minor constituents were isolated and identified from the petroleum ether fraction of Nephthea sp. The characterised compounds were screened and compared for their inhibitory potential against SARS-CoV-2 main protease (Mpro) using Autodock Vina and MOE software. Interestingly, most compounds were able to bind effectively to the active site of Mpro, of which nephthoside monoacetate (1); an acylated tetraprenyltoluquinol glycoside, exhibited the highest binding capacity in both software with comparable interaction energies to the ligand N3 and moderately acceptable drug-likeness properties, which drew attention to the relevance of marine-derived metabolites from Nephthea sp., particularly compound (1), to develop potential SARS-CoV-2 protease inhibitors.

Hyphaene thebaica (doum)-derived extract alleviates hyperglycemia in diabetic rats: a comprehensive in silico, in vitro and in vivo study.

In the present study, we investigated the hypoglycemic effect of different extracts (i.e. organic and aqueous) derived from the fruits of Hyphaene thebaica (doum) on male streptozotocin-induced diabetic rats. Blood glucose levels as well as the relative gene expression of insulin, TNF-α, and TGF-ß were determined in the pancreatic tissue of the experimental animals. Treatment of STZ-induced diabetic rats with aqueous extracts of the plant fruit over 7 weeks significantly reduced the elevated blood glucose and increased the relative expression of insulin, while the relative expression of inflammatory mediators (i.e. TNF-α and TGF-ß) was significantly reduced. Histopathological investigation also revealed that the aqueous extract treatment effectively reversed the ß-cell necrosis induced by STZ and restored its normal morphology. Furthermore, liquid chromatography high resolution mass spectrometry (LC-HRMS) and in silico chemical investigation of the aqueous extract elucidated its major bioactive phytochemicals (i.e. flavonoids) and putatively determined the pancreatic KATP channel as a target for these bioactive components. In vitro insulin secretion assay revealed that myricetin, luteolin, and apigenin were able to induce insulin secretion by human pancreatic cells (insulin production = 20.9 ± 1.3, 13.74 ± 1.8, and 11.33 ± 1.1 ng mL-1, respectively). Using molecular docking and dynamics simulations, we were able to shed the light on the insulin secretagogue's mode of action through these identified bioactive compounds and to determine the main structural elements required for its bioactivity. This comprehensive investigation of this native fruit will encourage future clinical studies to recommend edible and widely available fruits like doum to be a part of DM treatment plans.

Gas chromatography-mass spectrometry profiling and analgesic, anti-inflammatory, antipyretic, and antihyperglycemic potentials of Persea americana.

OBJECTIVES: The present study determines the chemical constituents of Persea americana using gas chromatography-mass spectrometry (GC-MS) and its different activities. MATERIALS AND METHODS: Air-dried powdered leaves of Persea americana were extracted by 95% methanol and fractionated consecutively with petroleum ether, chloroform, and ethyl acetate. The saponifiable matter, EtOAc and aqueous fractions were subjected to GC-MS. The analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties of extracts, different fractions, and crude polysaccharide were determined by hot plate, carrageenan-induced paw edema, yeast-induced pyrexia, and alloxan-induced hyperglycemia methods, respectively. RESULTS: Fourteen fatty acid methyl esters were identified in GC-MS-based profiling of the saponifiable matter. Alongside, 13 compounds were determined from EtOAc fraction and 6 compounds from the aqueous fraction of P. americana leaves. The ethyl acetate fraction and total stem extract displayed high anti-inflammatory potential with percentage of paw edema reduction by 48.99 and 47.54 %, respectively, compared with that of indomethacin (42.90 %). The ethyl acetate fraction and total stem extract revealed the highest analgesic activity with 137.95 and 137.12 % percent of protection against external stimulus, respectively. Investigation of antipyretic efficiency showed the total stem extract and crude polysaccharides attained normal temperature after 3 hr, which was very close to that of acetylsalicylic acid. The total leaf and stem extracts displayed significant antihyperglycemic activity with significant reduction in the level of blood glucose by 76.67 and 59.05 %, respectively. CONCLUSION: P. americana had analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties, which refer to its bioactive metabolites.

Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp. Metabolites: A Computational Study.

Since December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and serious health problems worldwide. In this study, we investigated 14 natural compounds isolated from Amphimedon sp. via a molecular docking study, to examine their ability to act as anti-COVID-19 agents. Moreover, the pharmacokinetic properties of the most promising compounds were studied. The docking study showed that virtually screened compounds were effective against the new coronavirus via dual inhibition of SARS-CoV-2 RdRp and the 3CL main protease. In particular, nakinadine B (1), 20-hepacosenoic acid (11) and amphimedoside C (12) were the most promising compounds, as they demonstrated good interactions with the pockets of both enzymes. Based on the analysis of the molecular docking results, compounds 1 and 12 were selected for molecular dynamics simulation studies. Our results showed Amphimedon sp. to be a rich source for anti-COVID-19 metabolites.

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Both ethyl acetate and aqueous fractions of Tabebuia aurea leaves exhibited noteworthy antioxidant and nephroprotective activities against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, as evidenced by the remarkable improvements of renal serum biomarkers and histopathological features. Additionally, the ethyl acetate fraction displayed a prominent in vitro antitrypanosomal activity against Trypanosoma brucei; consequently, the leaves were subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, ten metabolites were characterized, mostly dominated by flavonoids. Interestingly, two identified constituents viz., 3,9,12,15-octadecatetraenoic acid (9) and 9,11,13-octadecatrienoic acid (10) are reported firstly herein from the genus Tabebuia. Furthermore, among the dereplicated constituents, rutin (5) and kaempferol 3-O-rutinoside (6) exhibited the highest docking scores as effective antitrypanosomal compounds.

Local anaesthetic potential, metabolic profiling, molecular docking and in silico ADME studies of Ocimum forskolei, family Lamiaceae.

The present study aimed to detect the bioactive metabolites from Ocimum forskolei aerial parts which are responsible for the local anaesthetic activity of the ethyl acetate fraction. Following a bioassay-guided fractionation, twelve compounds were dereplicated from the ethyl acetate fraction which was the most potent one with a mean onset of action (1.43 ± 0.07****) min compared to tetracaine as a positive control (1.37 ± 0.07****) min. These compounds, along with seven other compounds (isolated by diverse chromatographic techniques) were subjected to a molecular docking study to declare the top scoring compounds predicted to be responsible for such activity. The results highlighted Rabdosiin and Apigenin-7-O-rutinoside as the main bioactive leaders of the local anaesthesia via forming multiple H- bonding with the sodium ion channels leading to their blockade and loss of pain sensation, which strongly supports the use of O. forskolei as a local anaesthetic agent.

Antiulcer potential and molecular docking of flavonoids from Ocimum forskolei Benth., family Lamiaceae.

The present study aimed to detect the bioactive metabolites from Ocimum forskolei aerial parts which are responsible for the antiulcer activity of the total ethanol extract (TEE) as well as different fractions (petroleum ether, dichloromethane, ethyl acetate and aqueous). Six flavonoids were isolated from the dichloromethane fraction which was the most potent; with an ulcer index value of 2.67 ± 2.18*** and % inhibition of ulcer of 97.7%; following a bioassay-guided fractionation. The isolated flavonoids were subjected to molecular docking analysis in an attempt to explain their significant antiulcer potential, and the results revealed that salvitin followed by sideritiflavone were the main active ones acting against M3 and H-2 receptors, respectively. Moreover, a molecular dynamics simulation illustrated the formation of two persistent H-bonds between salvitin and the two amino acids of the active site (Asn507 and Asp147) formed in 42 and 65% of the frames, respectively.

Chemical and biological studies on the soft coral Nephthea sp.

Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti-proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n-butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC50 values of 2.30 ± 0.07 and 3.12 ± 0.10 µg ml-1, respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC50 = 2.78 ± 0.09 µg ml-1). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC50 values of 0.72 ± 0.06 and 9.32 ± 0.57 µg ml-1, respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.