ABSTRACT
PURPOSE: Optical see-through head-mounted displays (OST-HMD) feature an unhindered and instantaneous view of the surgery site and can enable a mixed reality experience for surgeons during procedures. In this paper, we present a systematic approach to identify the criteria for evaluation of OST-HMD technologies for specific clinical scenarios, which benefit from using an object-anchored 2D-display visualizing medical information. METHODS: Criteria for evaluating the performance of OST-HMDs for visualization of medical information and its usage are identified and proposed. These include text readability, contrast perception, task load, frame rate, and system lag. We choose to compare three commercially available OST-HMDs, which are representatives of currently available head-mounted display technologies. A multi-user study and an offline experiment are conducted to evaluate their performance. RESULTS: Statistical analysis demonstrates that Microsoft HoloLens performs best among the three tested OST-HMDs, in terms of contrast perception, task load, and frame rate, while ODG R-7 offers similar text readability. The integration of indoor localization and fiducial tracking on the HoloLens provides significantly less system lag in a relatively motionless scenario. CONCLUSIONS: With ever more OST-HMDs appearing on the market, the proposed criteria could be used in the evaluation of their suitability for mixed reality surgical intervention. Currently, Microsoft HoloLens may be more suitable than ODG R-7 and Epson Moverio BT-200 for clinical usability in terms of the evaluated criteria. To the best of our knowledge, this is the first paper that presents a methodology and conducts experiments to evaluate and compare OST-HMDs for their use as object-anchored 2D-display during interventions.
Subject(s)
Data Display , Equipment Design , Orthopedic Procedures/instrumentation , User-Computer Interface , Computer Graphics , Head , HumansABSTRACT
Beta-boswellic acids are considered the main bioactive components of frankincense. Their potential to act as cytotoxic agents, as well as that of their derivatives remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-ß-boswellic acid (KBA) that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Monodesmosidic saponins of KBA are as cytotoxic as 3-acetyl-KBA. The presence of a free hydroxyl group at position C-3 seems to lower cytotoxicity while the presence of an amide function at C-24 improves cytotoxicity. The most active compound of this series gave IC50 values as low as 4.5 µM. Cell death proceeded mainly via apoptosis.
Subject(s)
Amides/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/pathology , Saponins/pharmacology , Triterpenes/pharmacology , Uterine Cervical Neoplasms/pathology , Amides/chemical synthesis , Amides/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Molecular Structure , Saponins/chemical synthesis , Saponins/chemistry , Structure-Activity Relationship , Triterpenes/chemistry , Uterine Cervical Neoplasms/drug therapyABSTRACT
Beta-boswellic acids are interesting triterpenoic acids that show different biological activities. Their cytotoxic potential, as well as that of their derivates remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-ß-boswellic acid that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Thus, the introduction of an amino group at position C-2 led to a significantly improved cytotoxic activity of amine 18. An apoptotic effect of compound 18 was determined using DNA laddering and trypan blue staining experiments.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship , Triterpenes/chemistryABSTRACT
Several novel alkylidene branched lupane derivatives have been prepared. Many of these compounds showed a significant cytotoxicity. The most active compound, 2-methylene-betulonic acid, showed IC(50) values between 0.2 and 0.6 µM for 15 different human cancer cell lines. Cytotoxicity can be improved by encapsulation in liposomes. These compounds act by triggering apoptotic cell death as shown by DNA-laddering experiments and acridine orange/ethidium bromide staining.
Subject(s)
Alkenes/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chemistry Techniques, Synthetic , Humans , Hydroxides/chemistry , Inhibitory Concentration 50 , Oxidation-Reduction , Triterpenes/chemistryABSTRACT
Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.
Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Sesquiterpenes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Colorimetry , Drug Screening Assays, Antitumor , Humans , Neoplasms/pathology , Rhodamines/chemistry , Sesquiterpenes/chemical synthesis , Sesquiterpenes/chemistry , Sesquiterpenes, Guaiane , Structure-Activity RelationshipABSTRACT
Novel betulin derivatives were prepared and tested for their antitumor activity. Starting from 3-O-acetyl- or 3-O-methyl-betulinic aldehyde, the synthesis of C-28 ethynyl derivatives was performed; their subsequent transformation with several 1,3-dipolarophiles afforded pyrazoles and 1,2,3-triazoles. Their screening for antitumor activity was performed in a panel of 15 human cancer cell lines by a colorimetric SRB-assay. Thereby, several compounds revealed a higher cytotoxicity than betulinic acid. In addition, the encapsulation of the lead structure 7 into liposomes was investigated. The results from a dye exclusion test and from DNA laddering experiments provided evidence for an apoptotic cell death.
Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Triterpenes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Colorimetry/methods , Drug Screening Assays, Antitumor , Fluorescent Dyes/chemistry , Humans , Liposomes , Neoplasms/pathology , Pentacyclic Triterpenes , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Pyrazoles/pharmacology , Rhodamines/chemistry , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry , Triazoles/pharmacology , Triterpenes/chemical synthesis , Triterpenes/chemistry , Betulinic AcidABSTRACT
Several novel betulin derivatives were prepared and evaluated for their antitumor activity. 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives. These compounds were further transformed into pyrazoles and 1,2,3-triazoles. Also, the synthesis of 3-amino substituted butenolides was carried out. The compounds were screened for their antitumor activity in a panel of 15 human cancer cell lines in a sulforhodamine B (SRB) assay. Several compounds showed a noteworthy antitumor activity. In addition, the possibility of encapsulation into liposomes was examined, thereby resulting in an increased cytotoxicity. The results from a trypan-blue test and from DNA laddering provided evidence for an apoptotic cell death.
Subject(s)
Antineoplastic Agents/chemical synthesis , Liposomes/chemistry , Triterpenes/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/toxicity , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Triterpenes/chemical synthesis , Triterpenes/toxicityABSTRACT
An endoperoxide was synthesized starting from 11-keto-beta-boswellic acid and screened for antitumor activity in a panel of 15 human cancer cell lines by an SRB assay. The compound induces apoptosis and shows an average IC(50) value of 0.4-4.5 microM.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Triterpenes/chemistryABSTRACT
The plant triterpenes betulin and betulinic acid (BA) are triterpenes featuring interesting pharmacological properties. Starting from substituted betulinic aldehydes, we used them as lead structures for the synthesis of several gamma-butyrolactones and butenolides. Their antitumor activity was examined for 15 cancer cell lines using a SRB-assay and their apoptotic action was documented by trypan-blue test and DNA laddering. Several compounds revealed a higher activity than betulinic acid.
Subject(s)
4-Butyrolactone/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Coloring Agents , DNA Fragmentation/drug effects , Drug Screening Assays, Antitumor , Humans , Oxidation-Reduction , Rhodamines , StereoisomerismABSTRACT
The reaction of betulinic aldehydes with various carbon nucleophiles gave a series of new betulin derivatives, among them epoxides, glycidic derivatives and beta-hydroxy carbonyl compounds. Subsequent transformations of the beta-hydroxy carbonyls lead to 1,3-diketo- and alpha,beta-unsaturated betulin derivatives. These compounds were assayed for cytotoxicity using 15 human cancer cell lines and a colorimetric SRB-assay. Several compounds revealed significant antitumour activity.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/pharmacology , Neoplasms/drug therapy , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Molecular Structure , Structure-Activity RelationshipABSTRACT
Starting from substituted 9-chloroacridines, a series of quinacrine and spacered dimeric acridine compounds was prepared. Their ability to interrupt the protein association of prion- and Alzheimer-specific proteins and Ab peptides was explored using a fast screening system based on FACS analysis. The bis-acridines displayed a higher activity than the corresponding monomers. Among these derivatives, best results were obtained with the 2,4-dimethoxy-6-nitro compound 7h for Abeta-peptides and the 2-methoxy-6-nitro compound 7f for PrP.
Subject(s)
Acridines/chemical synthesis , Acridines/therapeutic use , Alzheimer Disease/drug therapy , Prion Diseases/drug therapy , Acridines/pharmacology , Amyloid beta-Peptides/drug effects , Dimerization , Drug Evaluation, Preclinical/methods , Humans , In Vitro Techniques , Molecular Structure , Prions/drug effectsABSTRACT
A series of triterpene endoperoxides was synthesized and screened for antitumor activity in a panel of 15 human cancer cell lines by a sulforhodamine-B (SRB) assay. The compounds induce apoptosis and show excellent antitumor activity.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Peroxides/pharmacology , Triterpenes/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Inhibitory Concentration 50 , Molecular Structure , Peroxides/chemical synthesis , Structure-Activity Relationship , Triterpenes/chemical synthesisABSTRACT
The synthesis of dimeric compounds derived from quinazolin-2-one and 1,4-benzodiazepin-2-one possessing a piperazine or homopiperazine spacer was investigated. In addition, a piperazine spacered bis-isoalloxazine and a bis-riboflavin compound were prepared and their ability to interrupt the association of prion proteins and Alzheimer-specific Abeta peptides was investigated using a fast screening system based on flow cytometry. The bis-isoalloxazine 14 was identified as a new lead structure.
Subject(s)
Benzodiazepinones/chemical synthesis , Dimerization , Flavins/chemical synthesis , Protein Structure, Secondary/drug effects , Quinazolinones/chemical synthesis , Amyloid beta-Peptides/chemistry , Benzodiazepinones/pharmacology , Drug Evaluation, Preclinical/methods , Flavins/pharmacology , In Vitro Techniques , Molecular Structure , Prions/chemistry , Protein Array Analysis/methods , Quinazolinones/pharmacologyABSTRACT
A series of antiviral compounds consisting of an intercalating acridine derived part, a spacer region and a reactive EDTA-derived conjugate was synthesized in an easy sequence starting from 1,omega-alkyldiamines. As shown in model screenings, in the presence of ascorbic acid the Fe-complexes of these compounds reduced the phage-titer of MS2-phages by several logarithmic decades.
Subject(s)
Acridines/chemical synthesis , Antiviral Agents/chemical synthesis , Intercalating Agents/chemical synthesis , Levivirus/drug effects , Nucleic Acids/drug effects , Acridines/chemistry , Acridines/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Ascorbic Acid/metabolism , Edetic Acid/chemistry , Intercalating Agents/chemistry , Intercalating Agents/pharmacology , Iron/metabolismABSTRACT
A series of antiviral compounds consisting of an intercalating acridine derived part, a spacer region and a reactive EDTA derived conjugate was synthesized in an easy sequence starting from 1,omega-alkyldiamines. As shown in model screenings, in the presence of ascorbic acid the Fe-complexes of these compounds reduced the phage-titer of MS2-phages by >8 logarithmic decades.