Cytotoxic and Anti-Inflammatory Metabolites from the Soft Coral Scleronephthya gracillimum

Five new pregnane-type steroids, sclerosteroids J–N (1–5), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic analysis. Compound 4 exhibited cytotoxicity against HepG2, A549, and MDA-MB-231 cancer cell lines. Furthermore, steroids 2 and 4 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein, and 1, 2, 4 and 5 could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.     

Neritinaceramides A–E,New Ceramides from the Marine Bryozoan Bugula neritina Inhabiting South China Sea and Their Cytotoxicity

Five new ceramides, neritinaceramides A (1), B (2), C (3), D (4) and E (5), together with six known ceramides (6–11), two known alkyl glycerylethers (12 and 13) and a known nucleoside (14), were isolated from marine bryozoan Bugula neritina, which inhabits the South China Sea. The structures of the new compounds were elucidated as (2S,3R,3′S,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,3′-triol (1), (2S,3R,2′R,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,2′-triol (2), (2S,3R,2′R,4E,8E,10E)-2-(octadecanoylamino)-4,8,10-octadecatriene-l,3,2′-triol (3), (2S,3R,3′S,4E,8E)-2-(hexadecanoylamino)-4,8-octadecadiene-l,3,3′-triol (4) and (2S,3R,3′S,4E)-2-(hexadecanoylamino)-4-octadecene-l,3,3′-triol (5) on the basis of extensive spectral analysis and chemical evidences. The characteristic C-3′S hydroxyl group in the fatty acid moiety in compounds 1, 4 and 5, was a novel structural feature of ceramides. The rare 4E,8E,10E-triene structure in the sphingoid base of compounds 1–3, was found from marine bryozoans for the first time. The new ceramides 1–5 were evaluated for their cytotoxicity against HepG2, NCI-H460 and SGC7901 tumor cell lines, and all of them exhibited selective cytotoxicity against HepG2 and SGC7901 cells with a range of IC₅₀ values from 47.3 μM to 58.1 μM. These chemical and cytotoxic studies on the new neritinaceramides A–E (1–5) added to the chemical diversity of B. neritina and expanded our knowledge of the chemical modifications and biological activity of ceramides.     

Sesquiterpenoids from the Mangrove-Derived Aspergillus ustus 094102

Four new drimane sesquiterpenoids (1–4) and three known ones (5–7) were isolated from the fermentation broth of the mangrove-derived Aspergillus ustus 094102. Compound 5 was further resolved as four purified compounds 5a–5d. By means of extensive spectroscopic and ECD analysis as well as the chemical transformation, their structures were identified as (2R,3R,5S,9R,10S)-2,3,9,11-tetrahydroxydrim-7-en-6-one (ustusol F, 1), (2R,3R,5R,9S,10R)-2,3,11-trihydroxydrim-7-en-6-one (9-deoxyustusol F, 2), (3S,5R,9R,10R)-3,11,12-trihydroxydrim-7-en-6-one (ustusol G, 3), (5S,6R,9S,10S, 11R,2′E,4′E)-(11-dideoxy-11-hydroxystrobilactone A-6-yl)-5-carboxypenta-2,4-dienoate (ustusolate H, 4), ((5S,6R,9S,10S)-strobilactone A-6-yl) (2E,4E)-6,7-dihydroxyocta-2,4-dienoate (ustusolate I, 5), (2′E,4′E;6′,7′-erythro)-ustusolate I (5a) and (2′E,4′E;ent-6′,7′-erythro)-ustusolate I (5b), (2′E,4′E,6′R,7′R)-ustusolate I (5c) and (2′E,4′E,6′S,7′S)-ustusolate I (5d), (5S,6R,9S,10S,2′E,4′E)-(strobilactone A-6-yl)-5-carboxypenta-2,4-dienoate (ustusolate J, 6), and (2S,5S,9R,10S)-2,9,11-trihydroxydrim-7-en-6-one (ustusol B, 7), respectively. Compound 5 showed antiproliferation against the human tumor cells CAL-62 and MG-63 with the IC₅₀ values of 16.3 and 10.1 µM, respectively.     

Pseudaboydins A and B: Novel Isobenzofuranone Derivatives from Marine Fungus Pseudallescheria boydii Associated with Starfish Acanthaster planci

Two novel isobenzofuranone derivatives, pseudaboydins A (1) and B (2), along with five known compounds, including (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (3), (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-methoxybenzofuran (4), 3,3′-dihydroxy-5,5′-dimethyldiphenyl ether (5), 3-(3-methoxy-5-methylphenoxy)-5-methylphenol (6) and (−)-regiolone (7), were isolated from the culture broth of the marine fungus, Pseudallescheria boydii, associated with the starfish, Acanthaster planci. Their structures were elucidated primarily based on NMR and MS data. The absolute configurations of 1–4 were determined by CD spectroscopy and single-crystal X-ray diffraction studies. The cytotoxic and antibacterial activities of 1–4 were evaluated. Pseudaboydin A (1) showed moderate cytotoxic activity against human nasopharyngeal carcinoma cell line HONE1, human nasopharyngeal carcinoma cell line SUNE1 and human glandular lung cancer cell line GLC82 with IC₅₀ values of 37.1, 46.5 and 87.2 μM, respectively.     

Antibacterial and Antibiofilm Activities of Tryptoquivalines and Meroditerpenes Isolated from the Marine-Derived Fungi Neosartorya paulistensis,N. laciniosa,N. tsunodae,and the Soil Fungi N. fischeri and N. siamensis

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines l (1a), H (1b), F (1c), 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′]-2,2′-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a–d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.     

Towards the Small and the Beautiful: A Small Dibromotyrosine Derivative from Pseudoceratina sp. Sponge Exhibits Potent Apoptotic Effect through Targeting IKK/NFκB Signaling Pathway

A dibromotyrosine derivative, (1′R,5′S,6′S)-2-(3′,5′-dibromo-1′,6′-dihydroxy-4′-oxocyclohex-2′-enyl) acetonitrile (DT), was isolated from the sponge Pseudoceratina sp., and was found to exhibit a significant cytotoxic activity against leukemia K562 cells. Despite the large number of the isolated bromotyrosine derivatives, studies focusing on their biological mechanism of action are scarce. In the current study we designed a set of experiments to reveal the underlying mechanism of DT cytotoxic activity against K562 cells. First, the results of MTT cytotoxic and the annexin V-FITC/PI apoptotic assays, indicated that the DT cytotoxic activity is mediated through induction of apoptosis. This effect was also supported by caspases-3 and -9 activation as well as PARP cleavage. DT induced generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (MMP) as indicated by flow cytometric assay. The involvement of ROS generation in the apoptotic activity of DT was further corroborated by the pretreatment of K562 cells with N-acetyl-cysteine (NAC), a ROS scavenger, which prevented apoptosis and the disruption of MMP induced by DT. Results of cell-free system assay suggested that DT can act as a topoisomerase II catalytic inhibitor, unlike the clinical anticancer drug, etoposide, which acts as a topoisomerase poison. Additionally, we found that DT treatment can block IKK/NFκB pathway and activate PI3K/Akt pathway. These findings suggest that the cytotoxic effect of DT is associated with mitochondrial dysfunction-dependent apoptosis which is mediated through oxidative stress. Therefore, DT represents an interesting reference point for the development of new cytotoxic agent targeting IKK/NFκB pathway.     

Cellular Antioxidant Effect of Four Bromophenols from the Red Algae,Vertebrata lanosa

Three known bromophenols, 2,3-dibromo-4,5-dihydroxybenzylaldehyde (1), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-hydroxymethyldiphenylmethane (2) and bis(2,3-dibromo-4,5-dihydroxylbenzyl) ether (3), and one new one, 5,5″-oxybis(methylene)bis(3-bromo-4-(2′,3′-dibromo-4′,5′-dihydroxylbenzyl)benzene-1,2-diol) (4), were isolated from an extract of the red alga, Vertebrata lanosa. The antioxidant activity of these four bromophenols was examined using one biochemical and two cellular assays: Oxygen Radical Absorbance Capacity (ORAC), Cellular Antioxidant Activity (CAA) and Cellular Lipid Peroxidation Antioxidant Activity (CLPAA) assays. Compound 2 distinguished itself by showing potent activity, having a better antioxidant effect than luteolin in both the CAA and CLPAA assays and of quercetin in the CLPAA assay. Although several bromophenols are known to be potent antioxidants in biochemical assays, this is the first time their cellular antioxidant activity has been demonstrated.     

Rare Carbon-Bridged Citrinin Dimers from the Starfish-Derived Symbiotic Fungus Penicillium sp. GGF16-1-2

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD₅₀ values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).     

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1′-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1–10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI₅₀ values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.     

Discovery of GOT1 Inhibitors from a Marine-Derived Aspergillus terreus That Act against Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a devastating digestive system carcinoma with high incidence and death rates. PDAC cells are dependent on the Gln metabolism, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies. In this study, 18 butyrolactone derivatives (1–18) were isolated from a marine-derived Aspergillus terreus, and asperteretone B (5), aspulvinone H (AH, 6), and (+)-3′,3′-di-(dimethylallyl)-butyrolactone II (12) were discovered to possess significant GOT1-inhibitory activities in vitro, with IC₅₀ values of (19.16 ± 0.15), (5.91 ± 0.04), and (26.38 ± 0.1) µM, respectively. Significantly, the molecular mechanism of the crystal structure of GOT1–AH was elucidated, wherein AH and the cofactor pyrido-aldehyde 5-phosphate competitively bound to the active sites of GOT1. More importantly, although the crystal structure of GOT1 has been discovered, the complex structure of GOT1 and its inhibitors has never been obtained, and the crystal structure of GOT1–AH is the first reported complex structure of GOT1/inhibitor. Further in vitro biological study indicated that AH could suppress glutamine metabolism, making PDAC cells sensitive to oxidative stress and inhibiting cell proliferation. More significantly, AH exhibited potent in vivo antitumor activity in an SW1990-cell-induced xenograft model. These findings suggest that AH could be considered as a promising lead molecule for the development of anti-PDAC agents.     

A New Meroditerpene and a New Tryptoquivaline Analog from the Algicolous Fungus Neosartorya takakii KUFC 7898

A new meroditerpene sartorenol (1), a new natural product takakiamide (2) and a new tryptoquivaline analog (3) were isolated, together with nine known compounds, including aszonapyrone A, chevalone B, aszonalenin, acetylaszonalenin, 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, tryptoquivalines L, F and H, and the isocoumarin derivative, 6-hydroxymellein, from the ethyl acetate extract of the culture of the algicolous fungus Neosartorya takakii KUFC 7898. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and, in the case of sartorenol (1) and tryptoquivaline U (3), X-ray analysis was used to confirm their structures and to determine the absolute configuration of their stereogenic carbons. Compounds 1, 2 and 3 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, and multidrug-resistant isolates from the environment; however, none exhibited antibacterial activity (MIC ˃ 256 mg/mL). The three new compounds did not show any quorum sensing inhibition in the screening protocol based on the pigment production by Chromobacterium violaceum (ATCC 31532).     

Identification and Bioactivity of Compounds from the Mangrove Endophytic Fungus Alternaria sp.

Racemic new cyclohexenone and cyclopentenone derivatives, (±)-(4R*,5S*,6S*)-3-amino-4,5,6-trihydroxy-2-methoxy-5-methyl-2-cyclohexen-1-one (1) and (±)-(4S*,5S*)-2,4,5-trihydroxy-3-methoxy-4-methoxycarbonyl-5-methyl-2-cyclopenten-1-one (2), and two new xanthone derivatives 4-chloro-1,5-dihydroxy-3-hydroxymethyl-6-methoxycarbonyl-xanthen-9-one (3) and 2,8-dimethoxy-1,6-dimethoxycarbonyl-xanthen-9-one (4), along with one known compound, fischexanthone (5), were isolated from the culture of the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS (Mass), one and two dimensional NMR (nuclear magnetic resonance) spectroscopic data. Compounds 1 and 2 exhibited potent ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] scavenging activities with EC₅₀ values of 8.19 ± 0.15 and 16.09 ± 0.01 μM, respectively. In comparison to Triadimefon, compounds 2 and 3 exhibited inhibitory activities against Fusarium graminearum with minimal inhibitory concentration (MIC) values of 215.52 and 107.14 μM, respectively, and compound 3 exhibited antifungal activity against Calletotrichum musae with MIC value of 214.29 μM.     

Carijoside A,a Bioactive Sterol Glycoside from an Octocoral Carijoa sp. (Clavulariidae)

A new bioactive sterol glycoside, 3β-O-(3′,4′-di-O-acetyl-β-d-arabinopyranosyl) -25ξ-cholestane-3β,5α,6β,26-tetrol-26-acetate) (carijoside A, 1), was isolated from an octocoral identified as Carijoa sp. The structure of glycoside 1 was established by spectroscopic methods and by comparison with spectral data for the other known glycosides. Carijoside A (1) displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils and this compound exhibited moderate cytotoxicity toward DLD-1, P388D1, HL-60, and CCRF-CEM tumor cells.     

Bioactive Chaetoglobosins from the Mangrove Endophytic Fungus Penicillium chrysogenum

A novel chaetoglobosin named penochalasin I (1) with a unprecedented six-cyclic 6/5/6/5/6/13 fused ring system, and another new chaetoglobosin named penochalasin J (2), along with chaetoglobosins G, F, C, A, E, armochaetoglobosin I, and cytoglobosin C (3–9) were isolated from the culture of Penicillium chrysogenum V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and high resolution mass spectroscopic data. The absolute configuration of compounds 1 and 2 were determined by comparing the theoretical electronic circular dichroism (ECD) calculation with the experimental CD. Compound 1 was the first example, with a six-cyclic fused ring system formed by the connection of C-5 and C-2′ of the chaetoglobosin class. Compounds 5–8 remarkably inhibited the plant pathogenic fungus R. solani (minimum inhibitory concentrations (MICs) = 11.79–23.66 μM), and compounds 2, 6, and 7 greatly inhibited C. gloeosporioides (MICs = 23.58–47.35 μM), showing an antifungal activity higher than that of carbendazim. Compound 1 exhibited marked cytotoxicity against MDA-MB-435 and SGC-7901 cells (IC₅₀ < 10 μM), and compounds 6 and 9 showed potent cytotoxicity against SGC-7901 and A549 cells (IC₅₀ < 10 μM).     

The Chemically Highly Diversified Metabolites from the Red Sea Marine Sponge Spongia sp.

A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3β,5α-diol-6,5-olide (3); and an α,β-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2’-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 1–9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.     

Cytotoxic Polyketide Metabolites from a Marine Mesophotic Zone Chalinidae Sponge-Associated Fungus Pleosporales sp. NBUF144

Two new polyketide natural products, globosuxanthone F (1), and 2′-hydroxy bisdechlorogeodin (2), were isolated from the fungus Pleosporales sp. NBUF144, which was derived from a 62 m deep Chalinidae family sponge together with four known metabolites, 3,4-dihydroglobosuxanthone A (3), 8-hydroxy-3-methylxanthone-1-carboxylate (4), crosphaeropsone C (5), and 4-megastigmen-3,9-dione (6). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR and high-resolution electrospray ionization mass spectra (HRESIMS) data. The absolute configuration of 1 was further established by single-crystal X-ray diffraction studies. Compounds 1–5 were evaluated for cytotoxicity towards CCRF-CEM human acute lymphatic leukemia cells, and it was found that 1 had an IC₅₀ value of 0.46 µM.     

Amino Acid-Coupled Bromophenols and a Sulfated Dimethylsulfonium Lanosol from the Red Alga Vertebrata lanosa

Vertebrata lanosa is a red alga that can commonly be found along the shores of Europe and North America. Its composition of bromophenols has been studied intensely. The aim of the current study was therefore to further investigate the phytochemistry of this alga, focusing more on the polar components. In total, 23 substances were isolated, including lanosol-4,7-disulfate (4) and the new compounds 3,5-dibromotyrosine (12), 3-bromo-5-sulfodihydroxyphenylalanine (13), 3-bromo-6-lanosyl dihydroxyphenylalanine (14), 3-(6′-lanosyl lanosyl) tyrosine (15) and 5-sulfovertebratol (16). In addition, 4-sulfo-7-dimethylsulfonium lanosol (7) was identified. While, in general, the dimethylsulfonium moiety is widespread in algae, its appearance in bromophenol is unique. Moreover, the major glycerogalactolipids, including the new ((5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid 3′-[(6′’-O-α-galactopyranosyl-β-D-galactopyranosyl)]-1-glycerol ester (23), and mycosporine-like amino acids, porphyra-334 (17), aplysiapalythine A (18) and palythine (19), were identified.     

Nine New and Five Known Polyketides Derived from a Deep Sea-Sourced Aspergillus sp. 16-02-1

Nine new C₉ polyketides, named aspiketolactonol (1), aspilactonols A–F (2–7), aspyronol (9) and epiaspinonediol (11), were isolated together with five known polyketides, (S)-2-(2′-hydroxyethyl)-4-methyl-γ-butyrolactone (8), dihydroaspyrone (10), aspinotriol A (12), aspinotriol B (13) and chaetoquadrin F (14), from the secondary metabolites of an Aspergillus sp. 16-02-1 that was isolated from a deep-sea sediment sample. Structures of the new compounds, including their absolute configurations, were determined by spectroscopic methods, especially the 2D NMR, circular dichroism (CD), Mo₂-induced CD and Mosher’s ¹H NMR analyses. Compound 8 was isolated from natural sources for the first time, and the possible biosynthetic pathways for 1–14 were also proposed and discussed. Compounds 1–14 inhibited human cancer cell lines, K562, HL-60, HeLa and BGC-823, to varying extents.     

Cytotoxic,Cytostatic and HIV-1 PR Inhibitory Activities of the Soft Coral Litophyton arboreum

Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24(28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC₅₀ 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC₅₀s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned.