Accelerated biological aging as potential mediator mediates the relationship between pro-inflammatory diets and the risk of depression and anxiety: A prospective analysis from the UK biobank.

BACKGROUND: The relationship between inflammatory dietary patterns and the risk of depression/anxiety has not been clearly established due to differences in study populations, geographic regions, sex, and methods of calculating the inflammatory index. METHODS: We drew upon a prospective cohort in the UK Biobank and calculated the energy-adjusted dietary inflammatory index (E-DII). The follow-up time was defined from the date of completing the last dietary survey questionnaire to the date of diagnosis of depression, anxiety, phobic anxiety, other types of anxiety, death, loss to follow-up, or the respective censoring dates for England (September 30, 2021), Scotland (July 31, 2021), and Wales (February 28, 2018). The final follow-up times end on September 30, 2021, July 31, 2021, and February 28, 2018, for England, Scotland, and Wales, respectively. During the follow-up process, if a participant develops the condition, dies, or is lost to follow-up, the follow-up is terminated. We used Cox regression to evaluate the connection between E-DII and depression/anxiety. We employed restricted cubic spline curves for nonlinear relationships. We also conducted mediation analyses to explore whether biological age mediated the relationship between E-DII and depression. Additionally, we investigated whether genetic susceptibility modified the relationship between E-DII and depression through interaction modeling. RESULTS: In the final analysis, we included a total of 151,295, 159,695, 165,649, and 160,097 participants for the analysis of depression, all types of anxiety, specific phobia anxiety, and other types of anxiety, respectively. For every one-unit increase in E-DII, the risk of experiencing depression and anxiety increased by 5 % and 4 %, respectively. We identified a "J"-shaped nonlinear relationship (P for nonlinear = 0.003) for both depression and anxiety. A significant association with an elevated risk of depression was observed when E-DII exceeded 0.440, and an increased risk of anxiety was noted when E-DII was more than -0.196. Mediation analysis demonstrated that PhenoAge age acceleration (AA) (For depression, proportion of mediation = 9.6 %; For anxiety, proportion of mediation = 10.1 %) and Klemera-Doubal method Biological Age (KDM AA) (For depression, proportion of mediation = 2.9 %; For anxiety, proportion of mediation = 5.1 %) acted as mediators between E-DII and the development of depression and anxiety (P < 0.05). CONCLUSIONS: Diets with pro-inflammatory characteristics are associated with a heightened risk of depression and anxiety. Furthermore, the association of pro-inflammatory diets and depression is mediated by biological age.

Regulation of Tumor Apoptosis of Poriae cutis-Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways In Vitro.

Poria cocos is traditionally used as both food and medicine. Triterpenoids in Poria cocos have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased (p < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.

Aculeaxanthones A-E, new xanthones from the marine-derived fungus Aspergillus aculeatinus WHUF0198.

Introduction: Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A-E (4-8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4-4'-secalonic acid D (9), from different fermentation batches of the title fungus. Methods: A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1-9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay. Results and Discussion: The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4-8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1-9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 µg/mL, respectively.

Bacterial lipopolysaccharide induces settlement and metamorphosis in a marine larva.

How larvae of the many phyla of marine invertebrates find places appropriate for settlement, metamorphosis, growth, and reproduction is an enduring question in marine science. Biofilm-induced metamorphosis has been observed in marine invertebrate larvae from nearly every major marine phylum. Despite the widespread nature of this phenomenon, the mechanism of induction remains poorly understood. The serpulid polychaete Hydroides elegans is a well established model for investigating bacteria-induced larval development. A broad range of biofilm bacterial species elicit larval metamorphosis in H. elegans via at least two mechanisms, including outer membrane vesicles (OMVs) and complexes of phage-tail bacteriocins. We investigated the interaction between larvae of H. elegans and the inductive bacterium Cellulophaga lytica, which produces an abundance of OMVs but not phage-tail bacteriocins. We asked whether the OMVs of C. lytica induce larval settlement due to cell membrane components or through delivery of specific cargo. Employing a biochemical structure­function approach with a strong ecological focus, the cells and OMVs produced by C. lytica were interrogated to determine the class of the inductive compounds. Here, we report that larvae of H. elegans are induced to metamorphose by lipopolysaccharide produced by C. lytica. The widespread prevalence of lipopolysaccharide and its associated taxonomic and structural variability suggest it may be a broadly employed cue for bacterially induced larval settlement of marine invertebrates.

Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour.

Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC50 values of 2.61, 1.19, and 1.74 µM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 µg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC50 of 20.06 µM) and α-glycosidase inhibitor (IC50 of 17.18 µM), while tabernamine, ervahanine B, and ervadivaricatine B only showed α-glycosidase inhibitory activities with IC50 values in the range of 0.95-4.61 µM.

Aculeaquamide A, cytotoxic paraherquamide from the marine fungus Aspergillus aculeatinus WHUF0198.

A new paraherquamide named aculeaquamide A (1) was isolated from an EtOAc extract of Aspergillus aculeatinus WHF0198 culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compound 1 was confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines, Bel-7402, A549, and HCT-116. Compounds 1 and 2 showed cytotoxicity against Bel-7402 with IC50 values of 3.3 and 1.9 µM, respectively.

Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb.

Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and α-glucosidase.

Systematic identification of Ocimum sanctum sesquiterpenoid synthases and (-)-eremophilene overproduction in engineered yeast.

Plant-derived natural active products have attracted increasing attention for use in flavors and perfumes. These compounds also have applications in insect pest control because of their environment-friendly properties. Holy basil (Ocimum sanctum), a famous herb used in Ayurveda in India, is a natural source of medical healing agents and insecticidal repellents. Despite the available genomic sequences and genome-wide bioinformatic analysis of terpene synthase genes, the functionality of the sesquiterpene genes involved in the unique fragrance and insecticidal activities of Holy basil are largely unknown. In this study, we systematically screened the sesquiterpenoid biosynthesis genes in this plant using a precursor-providing yeast system. The enzymes that synthesize ß-caryophyllene and its close isomer α-humulene were successfully identified. The enzymatic product of OsaTPS07 was characterized by in vivo mining, in vitro reaction, and NMR detection. This product was revealed as (-)-eremophilene. We created a mutant yeast strain that can achieve a high-yield titer by adjusting the gene copy number and FPP precursor enhancement. An optimized two-stage fed-batch fermentation method achieved high biosynthetic capacity, with a titer of 34.6 g/L cyclic sesquiterpene bioproduction in a 15-L bioreactor. Further insect-repelling assays demonstrated that (-)-eremophilene repelled the insect pest, fall leafworm, suggesting the potential of (-)-eremophilene as an alternative to synthetic chemicals for agricultural pest control. This study highlights the potential of our microbial platform for the bulk mining of plant-derived ingredients and provides an impressive cornerstone for their industrial utilization.

Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system.

Angustmycin A has anti-mycobacterial and cytokinin activities, and contains an intriguing structure in which an unusual sugar with C5'-C6' dehydration is linked to adenine via an N-glycosidic bond. However, the logic underlying the biosynthesis of this molecule has long remained obscure. Here, we address angustmycin A biosynthesis by the full deciphering of its pathway. We demonstrate that AgmD, C, A, E, and B function as D-allulose 6-phosphate 3-epimerase, D-allulose 6-phosphate pyrophosphokinase, adenine phosphoallulosyltransferase, phosphoribohydrolase, and phosphatase, respectively, and that these collaboratively catalyze the relay reactions to biosynthesize angustmycin C. Additionally, we provide evidence that AgmF is a noncanonical dehydratase for the final step to angustmycin A via a self-sufficient strategy for cofactor recycling. Finally, we have reconstituted the entire six-enzyme pathway in vitro and in E. coli leading to angustmycin A production. These results expand the enzymatic repertoire regarding natural product biosynthesis, and also open the way for rational and rapid discovery of other angustmycin related antibiotics.

A New Fusicoccane-Type Norditerpene and a New Indone from the Marine-Derived Fungus Aspergillus aculeatinus WHUF0198.

A new norditerpene named aculeaterpene A (1) and a new indone named aculeaindone A (2), along with eight known compounds 3-10 were isolated from the culture extract of Aspergillus aculeatinus WHUF0198. The structural characterization of compounds 1 and 2 were performed by spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments, whereas the absolute configurations were determined by comparing their experimental or calculated ECD spectra. Compound 1 was the first report of fusicoccane-based norditerpene, in which the C-20 was degraded and tured into a hydroxy group.

Cytoprotection against Oxidative Stress by Methylnissolin-3-O-ß-d-glucopyranoside from Astragalus membranaceus Mainly via the Activation of the Nrf2/HO-1 Pathway.

Astragalus membranaceus is a famous herb found among medicinal and food plants in East and Southeastern Asia. The Nrf2-ARE assay-guided separation of an extract from Jing liqueur led to the identification of a nontoxic Nrf2 activator, methylnissolin-3-O-ß-d-glucopyranoside (MNG, a component of A. membranaceus). Nrf2 activation by MNG has not been reported before. Using Western Blot, RT-qPCR and imaging, we investigated the cytoprotective effect of MNG against hydrogen peroxide-induced oxidative stress. MNG induced the expression of Nrf2, HO-1 and NQO1, accelerated the translocation of Nrf2 into nuclei, and enhanced the phosphorylation of AKT. The MNG-induced expression of Nrf2, HO-1, and NQO1 were abolished by Nrf2 siRNA, while the MNG-induced expression of Nrf2 and HO-1 was abated and the AKT phosphorylation was blocked by LY294002 (a PI3K inhibitor). MNG reduced intracellular ROS generation. However, the protection of MNG against the H2O2 insult was reversed by Nrf2 siRNA with decreased cell viability. The enhancement of Nrf2 and HO-1 by MNG upon H2O2 injury was reduced by LY294002. These data showed that MNG protected EA.hy926 cells against oxidative damage through the Nrf2/HO-1 and at least partially the PI3K/Akt pathways.

Genome Mining Reveals a Multiproduct Sesterterpenoid Biosynthetic Gene Cluster in Aspergillus ustus.

Genome mining of Aspergillus ustus 094102 enabled the discovery of a multiproduct bifunctional terpene synthase (BTS), AuAS. Heterologous expression of AuAS led to the discovery of five new sesterterpenes, and coexpression of the upstream CYP450 monooxygenase (AuAP450) generated four new sesterterpene alcohols. Additionally, aspergilol A showed cytotoxic activities against MCF-7, MDA-MB231, and HepG2 cancer cells (IC50 21.20-48.76 µM), and aspergilol B exhibited a cytotoxic effect on MCF-7 cells (IC50 27.41 µM).

Two new guaiane sesquiterpenes from the fruiting bodies of Lactarius Deliciosus.

Two new guaiane sesquiterpenes, 7-(1-hydroxyethyl)-4-methyl-1-azulenecarboxaldehyde (1) and 7-isopropenyl-4-methyl-1-azulenecarboxylic acid (2), together with 5 known sesquiterpenes, were isolated from the fruiting bodies of Lactarius deliciosus. All structures were elucidated based on extensive spectroscopic methods, including 1 D and 2 D-NMR spectroscopy and high resolution mass spectrometry.

Uncommon terpenoids with anti-inflammatory activity from the Hainan soft coral Sinularia tumulosa.

One novel sesquiterpenoid containing an unprecedented eight-membered cyclic peroxide motif, sinulatumolin A (1), along with four new related terpenoids, namely sinulatumolins B-E (2-4 and 6), were isolated from South China Sea soft coral Sinularia tumulosa. The structures of all the isolates were elucidated by detailed spectroscopic analysis, chemical transformations, and single X-ray diffraction analysis. Compound 1 represents the first example of sesquiterpene bearing an eight-membered cyclic peroxide ring from soft coral. All the new compounds isolated were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4 and 6 displayed significant TNF-α inhibitory activity being comparable with that of the positive control dexamethasone (IC50 = 8.7 µM), with IC50 values of 7.5, 2.6, 5.5, and 3.6 µM, respectively.

Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells.

Parkinson's disease (PD) is a common dyskinesia disease, the mitochondrial unfolded protein response (mtUPR) may be directly or indirectly involved in the occurrence and development of PD, although the exact mechanism is unclear. We established a dopaminergic neuronal-like cell model of PD, by overexpression of PGC-1α to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1α and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24 h after MPP+ treatment in SH-SY5Y cells, which the protein and transcription levels of the proteases and molecular chaperones reached maximal. The proteases and molecular chaperones were significantly increased when overexpressed PGC-1α, which indicated that PGC-1α overexpression activated the mtUPR, and PGC-1α had a protective effect on SH-SY5Y cells. The expression levels of PGC-1α and LRPPRC were significantly improved in the PGC-1α overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1α overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1α may activate mtUPR, reducing the oxidative stress injury induced by MPP+ through LRPPRC signaling, thus maintain mitochondrial homeostasis.

Bioactive pterocarpans from Trigonella foenum-graecum L.

Trigonella foenum-graecum L. (fenugreek) is used as a leafy vegetable and spice in China and North African countries. However, the biochemical components of its aerial parts were rarely explored. In this study, the bioactivities of the various extract fractions from the aerial parts of this edible plant were assessed, the ethyl acetate extract fraction exhibited strong antioxidant and anti-inflammatory effects. Through bioassay-guided isolation, one new pterocarpan (1), as well as twelve known pterocarpans (2-13) were obtained, nine of them (5-13) were first reported in the fenugreek, four pterocarpans (9, 11-13) had strong antioxidant activity, eleven pterocarpans (1-3, 5-12) possessed obvious anti-inflammatory activity. This study indicates that pterocarpans are main bioactive components of this edible plant. Apart from its nutritional value as food, the aerial parts of this plant can also be further explored as functional foods or antioxidants in food industry.

Comparative Investigation into Formycin A and Pyrazofurin A Biosynthesis Reveals Branch Pathways for the Construction of C-Nucleoside Scaffolds.

Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond. However, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria and propose that their biosynthesis is likely initiated by a lysine N6-monooxygenase. Moreover, we show that forT and prfT (involved in FOR-A and PRF-A biosynthesis, respectively) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates 4-amino-3,5-dicarboxypyrazole and 3,5-dicarboxy-4-oxo-4,5-dihydropyrazole. We also decipher the enzymatic mechanism of ForT/PrfT for C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfT represents an example of ß-RFA-P (ß-ribofuranosyl-aminobenzene 5'-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics and also open the way for target-directed genome mining of PRF-A/FOR-A-related antibiotics.IMPORTANCE FOR-A and PRF-A are C-nucleoside antibiotics known for their unusual chemical structures and remarkable biological activities. Deciphering the enzymatic mechanism for the construction of a C-nucleoside scaffold during FOR-A/PRF-A biosynthesis will not only expand the biochemical repertoire for novel enzymatic reactions but also permit target-oriented genome mining of FOR-A/PRF-A-related C-nucleoside antibiotics. Moreover, the availability of FOR-A/PRF-A biosynthetic gene clusters will pave the way for the rational generation of designer FOR-A/PRF-A derivatives with enhanced/selective bioactivity via synthetic biology strategies.

Divergent Biosynthesis of C-Nucleoside Minimycin and Indigoidine in Bacteria.

Minimycin (MIN) is a C-nucleoside antibiotic structurally related to pseudouridine, and indigoidine is a naturally occurring blue pigment produced by diverse bacteria. Although MIN and indigoidine have been known for decades, the logic underlying the divergent biosynthesis of these interesting molecules has been obscure. Here, we report the identification of a minimal 5-gene cluster (min) essential for MIN biosynthesis. We demonstrated that a non-ribosomal peptide synthetase (MinA) governs "the switch" for the divergent biosynthesis of MIN and the cryptic indigoidine. We also demonstrated that MinCN (the N-terminal phosphatase domain of MinC), MinD (uracil phosphoribosyltransferase), and MinT (transporter) function together as the safeguard enzymes, which collaboratively constitute an unusual self-resistance system. Finally, we provided evidence that MinD, utilizing an unprecedented substrate-competition strategy for self-resistance of the producer cell, maintains competition advantage over the active molecule MIN-5'-monophosphate by increasing the UMP pool in vivo. These findings greatly expand our knowledge regarding natural product biosynthesis.

Spiroalanfurantones A-D, Four Eudesmanolide-Furan Sesquiterpene Adducts with a Pentacyclic 6/6/5/5/5 Skeleton from Inula helenium.

Spiroalanfurantones A-D (1-4), four eudesmanolide-furan sesquiterpene adducts with an unprecedented pentacyclic 6/6/5/5/5 skeleton, were isolated from the roots of Inula helenium. Their structures were elucidated by spectroscopic data analysis and single-crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1-4 is presented. Bioassay showed that compounds 1 and 2 significantly inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 17.3 and 9.5 µM, respectively.

Octahydro-Protoberberine and Protoemetine-Type Alkaloids from the Stems of Alangium salviifolium and Their Cytotoxicity.

Two octahydro-protoberberine alkaloids, alangiifoliumines A (1) and B (2), and two new protoemetine derivatives, alangiifoliumines C (3) and D (4), together with 11 known compounds, have been isolated from the stems of Alangium salviifolium. While the structures of these compounds were elucidated by spectroscopic methods, the absolute configurations of the new alkaloids were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism spectra calculations on selected stereoisomers. Compounds 1 and 2 represent the first 5,8,8a,9,12,12a,13,13a-octahydro-protoberberine derivatives, in which the aromatic ring D was reduced to cyclohexene. All the compounds isolated were evaluated for their cytotoxic activity against three human cancer cell lines: A-549, HeLa, and SKOV-3. Alkaloids 1, 3, and 6-14 exhibited inhibitory effects against all three human cancer cell lines, with half-maximal inhibitory concentration (IC50) values in the range of 3 nM to 9.4 µM.