Design, Synthesis and Evaluation of A Novel Teoptinib Derivative as an Effective Anti-Hepatocellular Carcinoma Agent.

BACKGROUND & PURPOSE: Hepatocellular Carcinoma (HCC) is a type of liver cancer known for its poor prognosis and high mortality. Teoptinib is a highly selective MET inhibitor that has been used in the treatment of liver cancer. Although good progress has been made in clinical treatment, further improvement is still needed. In this study, a series of novel Teoptinib derivatives were synthesized and evaluated as anti-cancer agents for the treatment of liver cancer, and an oral nanodrug delivery system was also explored. METHODS: A series of novel Teoptinib derivatives were synthesized, and an oral nanodrug delivery system was also explored. HPLC, high-resolution mass spectrometer and NMR were used to determine the structure and molecular formula of the synthesized compounds. Zeta potential assay was used to access the particle size distribution and zeta potential of the nanoparticles. MTT assay, cell colony formation assay, cell apoptosis inhibition assay, cell scratch assay, and the MHCC-97H xenograft model of nude mice assay were used to evaluate the in vitro and in vivo anti-tumor activity of the synthesized compounds. RESULTS: Compound (R)-10 showed the best antitumor activity with 0.010 µM of the IC50 value against MHCC-97H, a human liver cancer cell line with high c-Met expression. The MHCC-97H xenograft model of nude mice assay showed that nano-prodrug of compound (R)-10 exhibited good in vivo activity with 87.67% of the TGI at the dosage of 8 mg/kg. CONCLUSION: We designed and synthesized a series of c-Met inhibitors containing different side chains and chiral centers as anti-liver cancer agents. Among them, compound (R)-10 shows a promising effect as a lead molecule for further study in the treatment of liver cancer. The successful incorporation of (R)-10 into a novel oral nanodrug delivery system highlights the importance of effective drug delivery systems for enhanced therapeutic efficacy.

Genomic and Comparative Transcriptomic Analyses Reveal Key Genes Associated with the Biosynthesis Regulation of Okaramine B in Penicillium daleae NBP-49626.

Restricted production of fungal secondary metabolites hinders the ability to conduct comprehensive research and development of novel biopesticides. Okaramine B from Penicillium demonstrates remarkable insecticidal efficacy; however, its biosynthetic yield is low, and its regulatory mechanism remains unknown. The present study found that the yield difference was influenced by fermentation modes in okaramine-producing strains and performed genomic and comparative transcriptome analysis of P. daleae strain NBP-49626, which exhibits significant features. The NBP-49626 genome is 37.4 Mb, and it encodes 10,131 protein-encoding genes. Up to 5097 differentially expressed genes (DEGs) were identified during the submerged and semi-solid fermentation processes. The oka gene cluster, lacking regulatory and transport genes, displayed distinct transcriptional patterns in response to the fermentation modes and yield of Okaramine B. Although transcription trends of most known global regulatory genes are inconsistent with those of oka, this study identified five potential regulatory genes, including two novel Zn(II)2Cys6 transcription factors, Reg2 and Reg19. A significant correlation was also observed between tryptophan metabolism and Okaramine B yields. In addition, several transporter genes were identified as DEGs. These results were confirmed using real-time quantitative PCR. This study provides comprehensive information regarding the regulatory mechanism of Okaramine B biosynthesis in Penicillium and is critical to the further yield improvement for the development of insecticides.

Biocontrol Potential of Streptomyces odonnellii SZF-179 toward Alternaria alternata to Control Pear Black Spot Disease.

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of 'Hosui' and 'Wonwhang' pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.

Long-term application of silver nanoparticles in dental restoration materials: potential toxic injury to the CNS.

Silver nanoparticles (AgNPs) have durable and remarkable antimicrobial effects on pathogenic microorganisms, such as bacteria and fungi, in dental plaques. As such, they are widely added to dental restoration materials, including composite resins, denture bases, adhesives, and implants, to solve the problems of denture stomatitis, peri-implant inflammation, and oral infection caused by the long-term use of these dental restoration materials. However, AgNPs can be absorbed into the blood circulatory system through the nasal/oral mucosa, lungs, gastrointestinal tract, skin, and other pathways and then distributed into the lungs, kidneys, liver, spleen, and testes, thereby causing toxic injury to these tissues and organs. It can even be transported across the blood-brain barrier (BBB) and continuously accumulate in brain tissues, causing injury and dysfunction of neurons and glial cells; consequently, neurotoxicity occurs. Other nanomaterials with antibacterial or remineralization properties are added to dental restoration materials with AgNPs. However, studies have yet to reveal the neurotoxicity caused by dental restoration materials containing AgNPs. In this review, we summarize the application of AgNPs in dental restoration materials, the mechanism of AgNPs in cytotoxicity and toxic injury to the BBB, and the related research on the accumulation of AgNPs to cause changes of neurotoxicity. We also discuss the mechanisms of neurotoxicity caused by AgNPs and the mode and rate of AgNPs released from dental restorative materials added with AgNPs to evaluate the probability of neurotoxic injury to the central nervous system (CNS), and then provide a theoretical basis for developing new composite dental restoration materials. Mechanism of neurotoxicity caused by AgNPs: AgNPs in the blood circulation enter the brain tissue after being transported across the BBB through transendothelial cell pathway and paracellular transport pathway, and continuously accumulate in brain tissue, causing damage and dysfunction of neurons and glial cells which ultimately leads to neurotoxicity. The uptake of AgNPs by neurons, astrocytes and microglia causes damage to these cells. AgNPs with non-neurotoxic level often increases the secretion of a variety of cytokines, up-regulates the expression of metallothionein in glial cells, even up-regulates autophagy and inflammation response to protect neurons from the toxic damage of AgNPs. However, the protective effect of glial cells induced by AgNPs exposure to neurotoxic levels is insufficient, which leads to neuronal damage and dysfunction and even neuronal programmed cell death, eventually cause neurotoxicity.

The complete genome sequence of Pantoea agglomerans NBBC-01, isolated from rot potato tubers.

The Gram-negative bacterium Pantoea agglomerans has been isolated from various habitats including disease plants. Here, we present the genome of P. agglomerans strain NBBC-01 obtained from rotten potatoes that were infected by Ditylenchus desstructor. The genome information will prove advantageous in elucidating its ecological role.

[Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed. RESULTS: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia (OR=2.38), neutropenia (OR=2.2), anemia (OR=1.83) and hepatoxicity (OR=1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX. CONCLUSION: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.

Activation of peroxymonosulfate by palygorskite supported Co-Fe for water treatment.

In the present work, palygorskite (PAL) supported Co-Fe oxides (CoFe@PAL) were prepared and used as a peroxymonosulfate (PMS) activator for removal of rhodamine B (RhB) in water. The results showed that CoFe@PAL prepared at impregnation solution of 50 g L-1 and calcination temperature of 500 °C showed the best catalytic performance. The removal efficiency of RhB (10 mg L-1) by PMS (0.1 mmol L-1) activated with CoFe@PAL (1 g L-1) was above 98% within 60 min. The effects of various environmental factors including initial pH, humic acid (HA) and inorganic anions on the removal effect were simultaneously investigated. The radical quenching experiments and EPR characterization revealed that ˙OH, SO4˙-, O2˙- and 1O2 radicals existed in the CoFe@PAL/PMS system simultaneously. The intermediates during RhB degradation were analyzed by LC-MS and possible degradation pathways of RhB were proposed. Moreover, CoFe@PAL exhibited superior stability and reusability.

Novel Steroidal[17,16-d]pyrimidines Derived from Epiandrosterone and Androsterone: Synthesis, Characterization and Configuration-Activity Relationships.

Two series of novel steroidal[17,16-d]pyrimidines derived from natural epiandrosterone and androsterone were designed and synthesized, and these compounds were screened for their potential anticancer activities. The preliminary bioassay indicated that some of these prepared compounds exhibited significantly good cytotoxic activities against human gastric cancer (SGC-7901), lung cancer (A549), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), epiandrosterone, and androsterone. Especially the respective pairs from epiandrosterone and androsterone showed significantly different inhibitory activities, and the possible configuration-activity relationships have also been summarized and discussed based on kinase assay and molecular docking, which indicated that the inhibition activities of these steroidal[17,16-d]pyrimidines might obviously be affected by the configuration of the hydroxyl group in the part of the steroidal scaffold.

Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302.

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.

Antiviral Activity of Benzoheterocyclic Compounds from Soil-Derived Streptomyces jiujiangensis NBERC-24992

Pseudorabies virus (PRV) is a pathogen that causes Aujeszky's disease (AD) in animals, leading to huge economic losses to swine farms. In order to discover anti-PRV compounds, we studied the extracts of the strain Streptomyces jiujiangensis NBERC-24992, which showed significant anti-PRV activity. Eight benzoheterocyclic secondary metabolites, including three new compounds (1-3, virantmycins D-G) and five known compounds (4-8, virantmycin, A-503451 D, A-503451 D acetylate, A-503451 A, and A-503451 B), were isolated from the broth of NBERC-24992. The structures of the new compounds were identified by using extensive spectroscopic data, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compound 1 was found to be a novel heterocyclic compound with a tricyclic skeleton from natural product. All compounds were tested for antiviral activity, and 4 (virantmycin) showed an excellent effect against PRV and was better than ribavirin and acyclovir. Our study revealed that chlorine atom and tetrahydroquinoline skeleton were important active moiety for antiviral activity. Virantmycin could be a suitable leading compound for an antiviral drug against PRV.

Secondary Metabolites from Aspergillus sparsus NBERC_28952 and Their Herbicidal Activities.

Fungi have been used in the production of a wide range of biologically active metabolites, including potent herbicides. In the search for pesticides of natural origin, Aspergillus sparsus NBERC_28952, a fungal strain with herbicidal activity, was obtained. Chemical study of secondary metabolites from NBERC_28952 resulted in the isolation of three new asperugin analogues, named Aspersparin A-C (2-4), and a new azaphilone derivative, named Aspersparin D (5), together with two known compounds, Asperugin B (1) and sydonic acid (6). The structures of these compounds were elucidated based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. All of the isolated compounds were evaluated for their herbicidal activities on seedlings of Echinochloa crusgalli and Amaranthus retroflexus through Petri dish bioassays. Among them, compounds 5 and 6 exhibited moderate inhibitory activities against the growth of the roots and shoots of E. crusgalli seedlings in a dose-dependent manner, while 6 showed obvious inhibitory effect on seedlings of A. retroflexus, with an inhibitory rate of 78.34% at a concentration of 200 µg/mL. These herbicidal metabolites represent a new source of compounds to control weeds.

Plant-Associated Bacteria as Sources for the Development of Bioherbicides.

Weeds cause significant yield losses in crop production and influence the health of animals and humans, with some exotic weeds even leading to ecological crises. Weed control mainly relies on the application of chemical herbicides, but their adverse influences on the environment and food safety are a significant concern. Much effort has been put into using microbes as bioherbicides for weed control. As plant-associated bacteria (PAB), they are widely present in the rhizophere, inside crops or weeds, or as pathogens of weeds. Many species of PAB inhibit the seed germination and growth of weeds through the production of phytotoxic metabolites, auxins, hydrogen cyanide, etc. The performance of PAB herbicides is influenced by environmental factors, formulation type, surfactants, additives, application methods, and cropping measures, etc. These factors might explain the inconsistencies between field performance and in vitro screening results, but this remains to be clarified. Successful bioherbicides must be specific to the target weeds or the coinciding weeds. Detailed studies, regarding factors such as the formulation, application techniques, and combination with cultivation measures, should be carried out to maximize the performance of PAB-based bioherbicides.

Impact of posttransplant cyclophosphamide on the outcome of patients undergoing unrelated single-unit umbilical cord blood transplantation for pediatric acute leukemia.

BACKGROUND: Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia. METHODS: This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared. RESULTS: The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups. CONCLUSION: The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.

Acaricidal Activity and Field Efficacy Analysis of the Potential Biocontrol Agent Bacillus vallismortis NBIF-001 against Spider Mites.

In recent years, spider mites have caused considerable economic losses to global agriculture. However, currently available management strategies are limited because of the rapid development of resistance. In this study, Bacillus vallismortis NBIF-001 was isolated and evaluated for its acaricidal activity. NBIF-001 exhibited a significant lethal effect on spider mites within 48 h. The median lethal concentration (LC50) of the culture powders (3.2 × 1010 CFU/g) was 50.2 µg/mL for Tetranychus urticae (red form), 18.0 µg/mL for T. urticae (green form), and 15.7 µg/mL for Panonychus citri (McGregor). Cultivation optimisation experiments showed that when the number of spores increased, fermentation toxicity also increased. Moreover, field experiments demonstrated that NBIF-001 performed well in the biocontrol of P. citri, which showed a similar corrected field efficacy with the chemical control (67.1 ± 7.9% and 71.1 ± 6.4% after 14 days). Genomics analysis showed that NBIF-001 contains 231 factors and seven gene clusters of metabolites that may be involved in its acaricidal activity. Further bioassays of the fermentation supernatants showed that 50× dilution treatments killed 72.5 ± 5.4% of the mites in 48 h, which was similar with those of the broth. Bioassays of the supernatant proteins confirmed that various proteins exhibited acaricidal activity. Five candidate proteins were expressed and purified successfully. The bioassays showed that the small protein BVP8 exhibited significant acaricidal activity with an LC50 of 12.4 µg/mL (T. urticae). Overall, these findings suggest that B. vallismortis NBIF-001 is a potential biocontrol agent for spider mite management.

Diarylamine-Guided Carboxamide Derivatives: Synthesis, Biological Evaluation, and Potential Mechanism of Action.

Diarylamines are a class of important skeleton widely existing in drugs or natural products. To discover novel diarylamine analogues as potential drugs, two series of diamide and carboxamide derivatives containing diarylamine scaffold were designed, synthesized and evaluated for their potential cytotoxic activities. The bioassay results indicated that some of the obtained compounds (C5, C6, C7, C11) exhibited good cytotoxic effect on cancer cell lines (SGC-7901, A875, HepG2), especially, compound C11 present significantly selective proliferation inhibition activity on cancer and normal cell lines (MARC145). In addition, the possible apoptosis induction for highly potential molecules was investigated, which present compound C11 could be used as novel lead compound for discovery of promising anticancer agents.

1,4,6-trihydroxy-8-alkylated-9,10-anthraquinones with antibacterial activities from soil-derived Streptomyces sp. WS-13394.

Two new 1,4,6-trihydroxy-8-alkylated-9,10-anthraquinones (1-2) were isolated from the culture broth of the soil actinomycete Streptomyces sp. WS-13394. Their structures were elucidated on the basis of extensive spectroscopic analysis, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compounds 1 and 2, together with eight analogs (3-10), were evaluated for their antibacterial activities against five pathogens. The tested derivatives of alkylated anthraquinone exhibited selective activities to Gram-positive bacteria, while compounds 1 and 5 showed obvious activities against two zoonotic pathogens, Erysipelothrix rhusiopathiae and Streptococcus suis, with MIC values ranging from 3.13 to 12.5 µg ml-1.

Design, Synthesis, and Cytotoxic Activity of Novel Natural Arylsulfonamide-Inspired Molecules.

Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 µg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.

A pyruvate kinase deficiency child with novel PK-LR gene mutations was successfully cured by matched unrelated donor peripheral blood stem cell transplantation.

BACKGROUND: Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by a PK-LR gene mutation. Allogeneic hematopoietic cell transplantation (HCT) is an effective cure for PKD. However, the experience of applying HCT in PKD is limited. METHODS: We present a child with novel PK-LR gene mutations who was successfully cured by matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT). RESULTS: A 4-year-old, male patient suffered severe hemolytic anemia and jaundice 5 h after birth. Gene sequencing showed that the pyruvate kinase-liver and RBC (PK-LR) gene had a nonsense mutation in exon 5: c.602G>A (p.W201X), and large deletions in exons 3-9. Both of them were novel pathogenic mutations of the PK-LR gene. After transplantation, the hemoglobin level became normal and the nonsense mutation was undetectable. Grade Ⅳ acute graft-versus-host disease (aGVHD) and extensive chronic graft-versus-host disease (cGVHD) occurred in the patient. However, the GVHD was controlled effectively. The patient is alive and has good quality of life 22 months post-transplant, but has mild oral lichen planus-like lesion. CONCLUSION: Gene sequencing contributes to the diagnosis of PKD. HCT is an effective method for curing PKD, but we should explore how to reduce severe GVHD.

Selective and effective anticancer agents: Synthesis, biological evaluation and structure-activity relationships of novel carbazole derivatives.

Carbazole alkaloids is an important class of natural products with diverse biological functions. So, the aim of this article is to explore new chemical entities containing carbazole scaffold as potential novel cytotoxic agents based on our developed three-component indole-to-carbazole reaction. Two series of carbazole derivatives were designed and synthesized, and their in vitro cytotoxic activities against three cell lines (A875, HepG2, and MARC145) were evaluated. The results indicated that some of these carbazole derivatives exhibited significantly good cytotoxic activities against tested cell lines compared with the control 5-fluorouracil (5-FU). Especially, carbazole acylhydrazone compounds 7g and 7p displayed high inhibitory activity on cancer cells, but almost no activity on normal cells. Further analysis of induced apoptosis for potential compounds indicated that the potential antitumor agents induced cell death in A875 cells at least partly (initially) by apoptosis, which might be used as promising lead scaffold for discovery of novel carbazole-type cytotoxic agents.

Two new dipimprinine alkaloids from soil-derived Streptomyces sp. 44414B.

Two new dipimprinine alkaloids dipimprinine E (1) and dipimprinine F (2) were isolated from Streptomyces sp. 44414B. The structure was elucidated by extensive spectroscopic analysis, including ESI-MS, HR-MS, and 1D and 2D NMR experiments. Dipimprinines F (2) showed cytotoxic activities against three tumor cell lines, including A-875, Hep G2, and H-460, with IC50 values of 26.4, 0.5, and 9.0 µg ml-1, respectively.