RESUMEN
The tigliane ring system, which encompasses iconic members such as phorbol and TPA, is widely renowned due to numerous observations of displaying potent biological activity, and subsequent use as mainstream biochemical tools. Traditionally, naturally occurring phorboids are regarded as tumor promotors through PKC activation, although in recent times more highly oxidized natural derivatives have been identified as anti-tumor agents. In the view that only limited synthetic investigations toward skeletal stereochemical modification have been undertaken, non-natural systems could be useful for a better understanding of the tigliane pharmacophore via interrogation of cellular sensitivity. In this context the concise construction of a number of highly functionalized non-natural D-ring inverted phorbol esters were synthesized, via a rhodium-catalyzed [4+3] cycloaddition, and biologically evaluated using a range of cancer cell lines. The biological results highlight the notion that subtle changes in structure have dramatic effects on potency. Furthermore, although the non-natural derivatives did not outcompete the natural systems in the PKC-activation sensitive MCF7 cancer cell line, they outperformed in other cancer cell lines (MM96L and CAL27). This observation strongly suggested an alternate mode of action not involving activation of PKC, but instead involves thiol addition as indicated by glutathione addition and NF-κB reporter activity.
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Neoplasias , Forboles , Proteína Quinasa C/química , Compuestos de Sulfhidrilo/química , Línea Celular , HumanosRESUMEN
Structurally unique halimanes EBC-232 and EBC-323, isolated from the Australian rainforest plant Croton insularis, proved considerably difficult to elucidate. The two diastereomers, which consist an unusual oxo-6,7-spiro ring system fused to a dihydrofuran, were solved by unification and consultation of five in silico NMR elucidation and prediction methods [i.e., ACDLabs, olefin strain energy (OSE), DP4, DU8+ and TD DFT CD]. Structure elucidation challenges of this nature are prime test case examples for empowering future AI learning in structure elucidation.
RESUMEN
The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1nu and NOD/SCID mice and treated with intratumoral injection of 30 µg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Diterpenos/farmacología , Infiltración Neutrófila/efectos de los fármacos , Neoplasias de la Lengua/tratamiento farmacológico , Animales , Apoptosis , Carcinoma de Células Escamosas/patología , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Neoplasias de la Lengua/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Investigation of the Australian rainforest plant Croton insularis revealed seven new cis-, two new trans-cyclopropane casbanes, and the first trans-cyclopropane seco-casbane. The relative configuration of the cyclopropane moiety for all compounds (EBC-182, 217, 218, 220, 343, 357, 358, 361, 365, 373; EBC=EcoBiotics Compound) was assigned using 13 Câ NMR data. Comparison of the experimental electronic circular dichroism (ECD) spectra with the theoretical curves, calculated by TD-DFT at the B3LYP/6-31+G**//B3LYP/6-31+G** level, in conjunction with NOE data afforded the absolute configuration. EBC-180, 181 and 220 displayed potent activity against cervical carcinoma (HeLa cells).
RESUMEN
Antibacterial-activity-guided fractionation of a dichloromethane extract from the fruit of Cordyline manners-suttoniae and subsequent structure-activity investigations resulted in the identification of 10 new (1-10) and one known (11) 5α-spirostane saponin. The structures of the new compounds were established by 1D and 2D NMR analyses. The absolute configurations of the isolated compounds were determined by X-ray diffraction analysis or chemical derivatizations. The most active compound, suttonigenin F (6), inhibited the Gram-positive bacteria Staphylococcus aureus with MIC75 values that were comparable to those of the antibiotic chloramphenicol. Structure-activity relationships were also obtained from the assessment of antibacterial and cytotoxic activities of the isolated saponins.
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Antibacterianos/aislamiento & purificación , Cordyline/química , Saponinas/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Frutas/química , Humanos , Estructura Molecular , Extractos Vegetales/análisis , Saponinas/química , Saponinas/farmacología , Relación Estructura-ActividadRESUMEN
Investigation of the Australian rainforest plant Croton insularis led to isolation of the first casbane hydroperoxide diterpenes EBC-304 and EBC-320. Extensive DFT and electronic circular dichroism (ECD) calculations in combination with 2D NMR spectroscopy determined the absolute configurations. EBC-304 and EBC-320 both display significant cytotoxicity.
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Croton/química , Diterpenos/química , Peróxidos/química , Australia , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dicroismo Circular , Croton/metabolismo , Diterpenos/aislamiento & purificación , Diterpenos/toxicidad , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Peróxidos/aislamiento & purificación , Peróxidos/toxicidad , Bosque LluviosoRESUMEN
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
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Benceno/química , Anciano , Animales , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCIDRESUMEN
Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.
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Imagen Multimodal , Nanopartículas , Polímeros/síntesis química , Animales , Línea Celular Tumoral , Células Cultivadas , Radioisótopos de Flúor , Ratones , Microscopía Confocal , Nanopartículas/química , Polímeros/químicaRESUMEN
EBC-162 isolated from Croton insularis, obtained from the northern rainforest of Australia, was structurally affirmed as crotofolinâ C (4). Novel oxidative degradation products, EBC-233 and EBC-300, which are the first crotofolane endoperoxides, were also isolated. Both endoperoxides were found to be stable intermediates, which are proposed to undergo an unprecedented homo-Baeyer-Villiger biosynthetic rearrangement to give a new class of 1,14-seco-crotofolane diterpenes. Prolonged storage of all isolates assisted in authenticating their natural product status. Anticancer activities of reported compounds are presented.
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Croton/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Oxidación-Reducción , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
EBC-219 (4), isolated from Croton insularis (Baill), was established by spectroscopic and DFT methods as the first member of a new diterpene skeletal class, uniquely defined by the presence of a bicyclo[10.2.1] bridgehead olefin. The proposed biogenetic pathway to 4 from the co-isolated natural products EBC-131 (1), EBC-180 (2) and EBC-181 (3) is highly likely. EBC-180 (2) and EBC-181 (3) showed moderate to strong cytotoxic activity against various cancer cell lines.
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Productos Biológicos/química , Diterpenos/química , Australia , Productos Biológicos/aislamiento & purificación , Productos Biológicos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diterpenos/toxicidad , Células HT29 , Células HeLa , Humanos , Células K562 , Células MCF-7 , Espectroscopía de Resonancia Magnética , Conformación MolecularRESUMEN
BACKGROUND: Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.) injection of TT causes vascular disruption with concomitant tumor ablation in several preclinical models of cancer, in addition to various (sub)cutaneous tumors presenting in the veterinary clinic. TT has completed Phase I dose escalation trials, with some patients showing signs of abscopal effects. However, the exact molecular details underpinning its mechanism of action (MoA), together with its immunotherapeutic potential in oncology remain unclear. METHODS: A combination of microscopy, luciferase assays, immunofluorescence, immunoblotting, subcellular fractionation, intracellular ATP assays, phagocytosis assays and mixed lymphocyte reactions were used to probe the MoA of TT in vitro. In vivo studies with TT used MM649 xenograft, CT-26 and immune checkpoint inhibitor refractory B16-F10-OVA tumor bearing mice, the latter with or without anti-programmed cell death 1 (PD-1)/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb treatment. The effect of TT at injected and non-injected tumors was also assessed. RESULTS: Here, we show that TT induces the death of endothelial and cancer cells at therapeutically relevant concentrations via a caspase/gasdermin E-dependent pyroptopic pathway. At therapeutic doses, our data demonstrate that TT acts as a lipotoxin, binding to and promoting mitochondrial/endoplasmic reticulum (ER) dysfunction (leading to unfolded protein responsemt/ER upregulation) with subsequent ATP depletion, organelle swelling, caspase activation, gasdermin E cleavage and induction of terminal necrosis. Consistent with binding to ER membranes, we found that TT treatment promoted activation of the integrated stress response together with the release/externalization of damage-associated molecular patterns (HMGB1, ATP, calreticulin) from cancer cells in vitro and in vivo, characteristics indicative of immunogenic cell death (ICD). Confirmation of ICD in vivo was obtained through vaccination and rechallenge experiments using CT-26 colon carcinoma tumor bearing mice. Furthermore, TT also reduced tumor volume, induced immune cell infiltration, as well as improved survival in B16-F10-OVA tumor bearing mice when combined with immune checkpoint blockade. CONCLUSIONS: These data demonstrate that TT is an oncolytic small molecule with multiple targets and confirms that cell death induced by this compound has the potential to augment antitumor responses to immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Muerte Celular Inmunogénica , Animales , Ratones , Muerte Celular Inmunogénica/efectos de los fármacos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Línea Celular Tumoral , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapiaRESUMEN
Bone invasion is a common characteristic of oral squamous cell carcinoma (OSCC), with adverse affects on patient functionality and survival. Recent studies suggest that it is osteoclasts, rather than malignant keratinocytes themselves, which play the major role in facilitating the entry of the tumour into bone, and its progression within bone. Osteoclasts respond to a variety of local signalling pathways, initiated by products of the malignant epithelial cells. In the present review, we firstly introduce the clinical patterns of bone invasion, and then summarise these signalling pathways and their diverse roles in sequential phases of bone invasion. We also review current researches regarding the incidence and mechanisms of distant metastases to bone, and explain briefly the concept of epithelial-mesenchymal transition, which may generate cancer stem cells and initiate the bone invasion. Finally, we discuss more briefly approaches to the diagnosis and management of OSCC patients with bone invasion. With all these studies and some recent discoveries in our own laboratory, an enhanced understanding of bone invasion will be achieved, which should indicate potential molecular targets for future biotherapies.
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Neoplasias Óseas/secundario , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Transición Epitelial-Mesenquimal , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Phytochemical investigation of Chamaelirium luteum ("false unicorn") resulted in the isolation of 15 steroidal glycosides. Twelve of these (1, 2, 4-9, 11-13, and 15) are apparently unique to this species, and eight of these (6-9, 11-13, and 15) are previously unreported compounds; one (15) possesses a new steroidal aglycone. In addition, the absolute configuration of (23R,24S)-chiograsterol A (10) was defined, and its full spectroscopic characterization is reported for the first time. The structures and configurations of the saponins were determined using a combination of multistage mass spectrometry (MS(n)), 1D and 2D NMR experiments, and chemical degradation. The antiproliferative activity of nine compounds obtained in the present work, and eight related compounds generated in previous work, was compared in six human tumor cell lines, with aglycones 3 and 10 and related derivatives 16, 17, 19, and 20 all displaying significant antiproliferative activity.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Liliaceae/química , Plantas Medicinales/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Esteroides/aislamiento & purificación , Esteroides/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas/química , Saponinas/química , Esteroides/químicaRESUMEN
The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is an increasing clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here, we report a novel class of naturally occurring and semisynthetic epoxy-tiglianes, derived from the Queensland blushwood tree (Fontainea picrosperma), and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate EBC-1013 stimulated protein kinase C (PKC)-dependent neutrophil reactive oxygen species (ROS) induction and NETosis and increased expression of wound healing-associated cytokines, chemokines, and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodeling in acute thermal injuries in calves. In chronically infected diabetic mouse wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment, and complete healing (in six of seven wounds) with ordered keratinocyte differentiation. These results highlight a nonantibiotic approach involving contrasting, orthogonal mechanisms of action combining targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.
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Forboles , Animales , Antibacterianos/farmacología , Biopelículas , Bovinos , Humanos , Queratinocitos , Ratones , Cicatrización de HeridasRESUMEN
The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro. A subset of the 6,7-epoxytiglianes were efficacious against established tumors in mice; which generally correlated with in vitro activation of PKC. Importantly, epoxytiglianes without evidence of PKC activation showed limited antitumor efficacy. Taken together, these findings provide a strong rationale to reassess the role of PKC isoforms in cancer, and suggest in some situations their activation can be a promising strategy for anticancer drug discovery.
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Antineoplásicos/química , Antineoplásicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Proteína Quinasa C/metabolismo , Animales , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Ratones , Transducción de Señal/efectos de los fármacosRESUMEN
We previously identified the induction of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters: the prototypic PKC-activating drug TPA (12-O-tetradecanoylphorbol-13-acetate), and the novel compound PEP008 (20-O-acetyl-ingenol-3-angelate) in cell lines derived from melanoma, breast cancer and colon cancer. The diterpene esters induced permanent growth arrest with characteristics of senescence in a subset of cell lines in all three solid tumor models at 100-1000 ng/ml. Use of the PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling identified pivotal genes involved in DNA synthesis and cell cycle control down-regulated by treatment in all three sensitive tumor models. At the protein level, prolonged down-regulation of E2F-1 and proliferating cell nuclear antigen (PCNA), sustained expression of p21(WAF1/CIP1) and dephosphorylation of retinoblastoma (Rb) occurred in the sensitive cells. Additionally, the type II tumor suppressor HRASLS3, which has a role in mitogen-activated protein kinase (MAPK) pathway suppression, was constitutively elevated in cell lines resistant to the senescence effects compared to their sensitive counterparts. Together, these results demonstrate that both TPA and the novel PKC-activating drug PEP008 induce growth arrest with characteristics of senescence in solid tumor cell lines derived from a variety of tissue types, and by a similar mechanism. PKC-activating diterpene esters may therefore have therapeutic potential in a subset of breast cancer, colon cancer and melanoma tumors.
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Senescencia Celular/efectos de los fármacos , Diterpenos/farmacología , Activadores de Enzimas/farmacología , Ésteres/farmacología , Neoplasias/enzimología , Neoplasias/patología , Proteína Quinasa C/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Isoenzimas/metabolismo , Neoplasias/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Fosfolipasas A2 Calcio-Independiente , Acetato de Tetradecanoilforbol/farmacología , Transcripción Genética/efectos de los fármacos , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , beta-Galactosidasa/metabolismoRESUMEN
A detailed examination of [4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo compounds revealed that 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) reacts to form either 2,3- or 3,4-disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8-disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa-2,4-diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.
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Antineoplásicos/síntesis química , Compuestos Azo/química , Compuestos Bicíclicos con Puentes/síntesis química , Diterpenos/síntesis química , Microondas , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Ciclización , Humanos , Modelos Moleculares , Estructura Molecular , Estereoisomerismo , Triazoles/químicaRESUMEN
Skin cancer is a broad term used to describe a number of different malignant indications of the skin. Skin cancers mostly comprise of the keratinocyte cancers [Basal Cell Carcinoma (BCC) and cutaneous Squamous Cell Carcinoma (SCC)], and melanoma. Surgical excision of these malignancies has been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including co-morbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances. Topical treatment potentially allows for higher drug levels at the tumor site, and may result in less overall toxicity than systemic agents. This review will specifically address the current agents used in topical treatment of skin cancers, and introduce emerging treatments from the natural product field that may also find utility in these indications.
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Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Administración Cutánea , Antineoplásicos/administración & dosificación , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Ensayos Clínicos como Asunto , Diterpenos/farmacología , Diterpenos/uso terapéutico , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Peca Melanótica de Hutchinson/tratamiento farmacológico , Peca Melanótica de Hutchinson/patología , Imiquimod/farmacología , Imiquimod/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/patología , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias de Células Escamosas/tratamiento farmacológico , Neoplasias de Células Escamosas/patología , Fotoquimioterapia/efectos adversos , Fotoquimioterapia/métodos , Retinoides/farmacología , Retinoides/uso terapéutico , Piel/fisiopatología , Rayos Ultravioleta/efectos adversosRESUMEN
Acronychia crassipetala is an endemic plant species in Australia. Its phytochemistry and therapeutic properties are underexplored. The hexane extract of the fruit A. crassipetala T. G. Hartley was found to inhibit the growth of the Gram-positive bacteria Staphylococcus aureus. Following bio-activity guided fractionation, two prenylated acetophenones, crassipetalonol A (1) and crassipetalone A (2), were isolated. Their structures were determined mainly by NMR and MS spectroscopic analyses. This is the first record of the isolation and structural characterisation of secondary metabolites from the species A. crassipetala. Their antibacterial and cytotoxic assessments indicated that the known compound (2) had more potent antibacterial activity than the antibiotic chloramphenicol, while the new compound (1) showed moderate cytotoxicity.