Preface to COAST 2018 Innovators' Workshop: Bridging the biology and technology gap in orthodontics and craniofacial care.

OBJECTIVE: A third focused workshop explored how to transfer novel findings into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Participants met at the Scottsdale Plaza Resort, 12-16 September 2018 for the Consortium for Orthodontic Advances in Science and Technology 2018 Innovators' Workshop. Thirty speakers and four lunch-hour focus group leaders shared and exchanged information with approximately 45 registered attendees. MATERIAL AND METHODS: This Innovators' Workshop was organized according to five themed sessions which covered: (a) The relevance of genetics, biology and environment to therapeutic outcomes; (b) Application of bioinformatics in craniofacial research; (c) Regeneration with and for orthodontic treatment; (d) Technology in precision orthodontics; and (e) Muscle, joint, and airway: Growth, function and pain. RESULTS: The papers that comprise this supplemental issue exemplify the important outcomes of the 2018 COAST Workshop. In addition, matters identified as important needs include improved understanding of neural, skeletal and muscle tissue crosstalk in early craniofacial growth; standardized methods for three-dimensional radiographic and surface landmark and reference plane identification, measurements and serial superimpositioning techniques for use in the clinic; sharing and making available existing data sets (eg, cone beam computed tomography images, genotype-phenotype data); evidence of the usefulness and effectiveness of new devices; guidelines of what to measure to characterize the airway; more information about the influences of the soft tissues on craniofacial morphology; and information about effective digital work flows applied to clinical and educational settings. CONCLUSIONS: Progress in bridging the biology-technology gap has identified new needs for improvements in orthodontics and craniofacial care.

Early Weight Gain in Infants With Cleft Lip and Palate Treated With and Without Nasoalveolar Molding: A Retrospective Study.

OBJECTIVE: To assess weight gain of infants with cleft lip and/or palate (CL ± P) treated with nasoalveolar molding (NAM). DESIGN: Retrospective, case-control chart review. SETTING: Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon. PATIENTS, PARTICIPANTS: Infants with nonsyndromic CL ± P and noncleft controls. INTERVENTIONS: Prior to primary lip surgery, NAM was either included (+NAM) or not included (-NAM) in the cleft treatment protocol. MAIN OUTCOME MEASURE(S): Weight gain and percentage weight gain relative to initial weight were compared among +NAM, -NAM, and control groups from birth to 7 months and from birth to 36 months. RESULTS: Comparing +NAM and -NAM groups, no significant difference in weight or percentage weight gain was found in either time window. Compared to controls, from birth to 7 months, both CL ± P groups weighed less (P < .001), while percentage weight gain was greater for the +NAM (P < .001) and did not differ for -NAM. From birth to 36 months relative to controls, weight for +NAM showed no significant difference and -NAM weighed less (P < .01), while percentage weight gain was greater for both CL ± P groups (P < .001). CONCLUSIONS: Comparisons of CL ± P infants treated with and without NAM showed that with the NAM appliance, despite its added complexity, there was no adverse impact on weight gain. Comparisons to noncleft, control infants suggests that NAM treatment may have a beneficial impact on weight gain.

Characterization of the murine macrophage response to infection with virulent and avirulent Burkholderia species.

BACKGROUND: Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered. RESULTS: The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt. CONCLUSIONS: These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.

Steroidal alkaloids from the marine sponge Corticium niger that inhibit growth of human colon carcinoma cells.

Bioinformatic analysis of data from the NCI-60 cell cytotoxicity screen revealed a subset of extracts that showed selective cytotoxic activity toward human colon carcinoma cell lines. Bioassay-guided fractionation of a colon cancer selective extract from a Philippines collection of the marine sponge Corticium niger provided two new steroidal alkaloids, plakinamines N (1) and O (2), along with two known compounds of the plakinamine class (3, 4). The structures of these compounds were elucidated by interpretation of combined MS and NMR spectroscopic data. Plakinamines N (1), O (2), and J (4) were tested for antiproliferative activity in the NCI-60 screen, and they showed enhanced inhibitory effects against all of the colon cell lines with mean GI50 values of 11.5, 2.4, and 1.4 µM, respectively.

Growth inhibition of human colon carcinoma cells by sesquiterpenoids and tetralones of Zygogynum calothyrsum.

Bioassay-guided phytochemical investigation of Zygogynum calothyrsum using the human colon carcinoma cell lines COLO205 and KM12 led to the isolation of three new drimane-type sesquiterpenoids, 1ß-p-hydroxy-E-cinnamoyldrimeninol (1), 1ß-p-hydroxy-E-cinnamoyl-5α-hydroxydrimeninol (2), and methyl ether of 1ß-p-hydroxy-E-cinnamoyl-12α-methoxydrimeninol (3). Also isolated was the known 1ß-p-coumaroyloxypolygodial (4) together with two new tetralones, 3'-deoxyisozygolone A (5) and calothyrlone A (9), three known tetralones, isozygolone A (6), zygolone A (7), and 4'-O-methylzygolone A (8), and a known cinnamolide (10). Compounds 1, 7, and 8 demonstrated higher cytotoxicity against COLO205 (GI50 18, 17, and 11 µM, respectively) and KM12 (GI50 14, 14, and 17 µM, respectively) than the other compounds.

Comparison of GUMMETAL® and stainless steel alloy during canine retraction: A pilot split-mouth randomized controlled trial.

OBJECTIVES: A TiNb alloy wire (GUMMETAL® [GM], Toyota Central R&D Labs, Inc., Nagakute, Japan) was recently developed with unique properties for orthodontic applications. This pilot split-mouth randomized controlled trial compared maxillary canine retraction during space closure using sliding mechanics on GM vs. stainless steel (SS) archwires. METHODS: Subjects who met the inclusion criteria were treated with fixed appliances and maxillary first-premolar extractions between September 2020 and March 2022. After leveling and aligning, maxillary archwires, fabricated by crimping together segments of 0.016×0.022" GM and SS archwires, were placed and canine retraction initiated using nickel-titanium coil springs. Digital models of the maxillary arch were superimposed at 0, 4, 8 and 12 weeks and the amount of canine movement (mm), rate of movement (mm/month), and 3-dimensional changes (rotational, vertical extrusion, tip) were measured and compared statistically. RESULTS: Of the 12 subjects recruited, only six completed the study with a median age of 15.8 years (12.0-17.4 years). At 12 weeks, the median canine retraction was 3.41mm (IQR: 2.10, 4.76) with GM versus 3.71mm (IQR: 1.62, 6.45) with SS. The retraction rate was 1.14mm/month (IQR: 0.69, 1.59) with GM, versus 1.24mm/month (IQR: 0.54, 2.15) with SS. The median rotational, vertical and tip changes of the canine were 7.90̊, 0.59mm and 6.15̊ with GM, and 7.25̊, 0.29mm and 2.05̊ with SS. Intergroup differences with all measurements were not statistically significant. CONCLUSION: No significant differences were found between GM and SS during maxillary canine retraction. GM demonstrated clinical potential for space closure mechanics, however, future larger studies are needed.

Efficacy of CPP-ACP fluoride varnish applied with and without acid etching in preventing enamel demineralization compared to light-curable fluoride varnish.

OBJECTIVES: To compare efficacy of casein phosphopeptide (CPP)-amorphous calcium phosphate (ACP) fluoride varnish and light-curable resin modified glass ionomer fluoride varnish (FV) in preventing white spot lesions and evaluating acid etching prior to CPP-ACPFV application on its efficacy. MATERIALS AND METHODS: Molars and premolars were transected and halves divided into four groups (n = 18/group): (1) resin-modified glass ionomer FV: etched and Clinpro-XT varnish (3M ESPE, Pymble, New South Wales, Australia) application; (2) CPP-ACPFV: MI varnish (GC America, Alsip, IL) application; (3) Etch+CPP-ACPFV: etched and MI varnish application; (4) Control: etched and no surface treatment. To simulate 12 weeks in an intraoral environment, samples were subjected to thermocycling, brushing, and pH cycling. Enamel surface microhardness was evaluated at baseline and after the simulated 12 weeks. Representative samples were also assessed using scanning electron microscopy (SEM). RESULTS: At baseline there was no significant difference in microhardness among groups. After the simulated 12 weeks, all groups showed significant within-group differences (P < .001). Control showed the highest percentage loss of surface microhardness (89%), followed by CPP-ACPFV (58%), RMGIFV (51%), and Etch+CPP-ACPFV (24%). The control group had a significant decrease in microhardness compared to all experimental groups (P < .001). No difference was found between the RMGIFV and CPP-ACPFV varnish groups. The Etch+CPP-ACPFV group had significantly less decrease in microhardness compared to the RMGIFV (P < .001) and CPP-ACPFV groups (P < .001). With SEM, control samples showed signs of enamel surface damage, while experimental groups showed spherical particles on a relatively intact surface. CONCLUSIONS: RMGIFV and CPP-ACPFV are effective in reducing enamel demineralization. Acid etching the enamel surface prior to CPP-ACPFV varnish application increased its efficacy.

Shear Bond Strength and Bracket Base Morphology of New and Rebonded Orthodontic Ceramic Brackets.

The objectives of this study were to (1) to evaluate the shear bond strength (SBS) of two ceramic brackets when new and when rebonded following various bracket base conditioning methods, and (2) to determine bond failure mode relative to bracket base morphology. 100 Symetri ClearTM (SC) and 100 Radiance Plus® (RP) ceramic brackets were bonded to bovine incisors and divided into five groups: one group served as controls and four had brackets rebonded following conditioning by: no surface treatment, sealant, sandblasting, and flame then steam. SBS, adhesive remnant index, and bracket base morphology were evaluated. SBS showed no statistical difference between new and rebonded with no surface treatment or sealant (SC brackets) and with sealant or flame and steam (RP brackets). When comparing SC to RP, SBS was higher with SC, no surface treatment, and sandblasted groups. All groups had varying amounts of adhesive left on the tooth, with the sandblasted group having the most. SEM analysis showed that sandblasting damaged the retention features of bracket bases. In conclusion, when rebonded, the SBS of SC brackets that had no surface treatment and both SC and RP brackets that had sealant showed no significant differences to new brackets. Sandblasting damaged the retention features of SC and RP bracket bases, resulting in low SBS.

Association between obstructive sleep apnea syndrome and bone mineral density in adult orthodontic populations.

OBJECTIVE: To determine the association between obstructive sleep apnea syndrome (OSAS) and predicted bone mineral density (BMD) in adults presenting for orthodontic treatment. METHODS: This retrospective cross-sectional study included 38 adults divided into OSAS and non-OSAS groups. Using pre-treatment CBCT images, radiographic density (RD) of left and right lateral regions of the 1st cervical vertebrae and dens of the 2nd cervical vertebrae were measured as an indicator for BMD. RESULTS: When controlling for age, sex, and BMI, the mean RD was significantly lower in the OSAS group compared to the non-OSAS group (left CV1: 36.69 ± 84.50 vs. 81.67 ± 93.25 Hounsfield Units [HU], respectively, p = 0.031; right CV1: 30.59 ± 81.18 vs. 74.26 ± 91.81 HU, p = 0.045; dens: 159.25 ± 115.96 vs. 223.94 ± 106.09 HU, p = 0.038). CONCLUSION: Adults with OSAS have lower values for predicted BMD than those without OSAS.

Comparison of bleaching effects when applied to white-spot lesions before or after resin infiltration: An in vitro study.

BACKGROUND: The purpose of this study was to compare color alterations (ΔE) of white-spot lesions (WSLs) bleached before versus after resin infiltration (RI). METHODS: Using the facial surfaces of bovine maxillary incisors, WSLs were created and the teeth were allocated into 2 groups (n = 45/group): bleach then RI (B-RI group) and RI then bleach (RI-B group). To determine ΔE, Commission Internationale de l'Eclairage L∗ a∗ b∗ (L∗ represents lightness, ranging from black to white [0-100]; a∗ represents green to red chromaticity [-150-+100]; and b∗ represents blue to yellow chromaticity [-100-+150]) measurements were obtained at baseline, after WSL formation, and after RI and bleaching. Representative specimens were evaluated by means of scanning electron microscopy. Statistical analyses included the Mann-Whitney U and Wilcoxon signed rank tests (P ≤ .0016) and repeated measures analysis of variance (P ≤ .05). RESULTS: No differences in ΔE were found comparing B-RI with RI-B groups or when the B-RI group was compared with bleached enamel. A statistically significant difference was found when the RI-B group was compared with bleached enamel (ΔE, 0.81; P < .001), but the difference was deemed not clinically significant. Scanning electron microscopy revealed that bleaching after RI increased surface roughness of the resin. CONCLUSIONS: There were no clinically significant differences in ΔE of WSLs when bleach was applied before or after RI; however, applying bleaching agent after RI roughened the surface of the resin material. PRACTICAL IMPLICATIONS: Results indicate that ΔE were not clinically significantly different between WSLs bleached before versus after RI, although it is best to sequence bleaching before RI therapy, as bleaching after RI roughened the restoration's surface.

Accuracy and reliability of buccal bone height and thickness measurements from cone-beam computed tomography imaging.

INTRODUCTION: Cone-beam computed tomography (CBCT) imaging has broadened opportunities for examining morphologic aspects of the craniofacial complex, including alveolar bone, but limitations of the technology have yet to be defined. Through the use of comparisons with direct measurements, the purpose of this study was to investigate the accuracy and reliability of buccal alveolar bone height and thickness measurements derived from CBCT images. METHODS: Twelve embalmed cadaver heads (5 female, 7 male; mean age: 77 years) were scanned with an i-CAT 17-19 unit (Imaging Sciences International, Hatfield, Pa) at 0.3 mm voxel size. Buccal alveolar bone height and thickness measurements of 65 teeth were made in standardized radiographic slices and compared with direct measurements made by dissection. All measurements were repeated 3 times by 2 independent raters and examined for intrarater and interrater reliability. Measurement means were compared with 2-tailed t tests. Agreement between direct and CBCT measurements was assessed by concordance correlation coefficients, Pearson correlation coefficients, and Bland-Altman plots. RESULTS: Intrarater reliability was high as were interrater correlations for all measurements (≥0.97) except CBCT buccal bone thickness (0.90). CBCT measurements did not differ significantly from direct measurements, and there was no pattern of underestimation or overestimation. The mean absolute differences were 0.30 mm in buccal bone height and 0.13 mm in buccal bone thickness with 95% limits of agreement of -0.77 to 0.81 mm, and -0.32 to 0.38 mm, respectively. Agreement between the 2 methods was higher for the measurements of buccal bone height than buccal bone thickness, as demonstrated by concordance correlation coefficients of 0.98 and 0.86, respectively. CONCLUSIONS: For the protocol used in this study, CBCT can be used to quantitatively assess buccal bone height and buccal bone thickness with high precision and accuracy. Comparing the 2 sets of CBCT measurements, buccal bone height had greater reliability and agreement with direct measurements than did the buccal bone thickness measurements.

Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.

A joint analysis of the NCI60 small molecule screening data, their genetically defective genes, and mechanisms of action (MOA) of FDA approved cancer drugs screened in the NCI60 is proposed for identifying links between chemosensitivity, genomic defects and MOA. Self-Organizing-Maps (SOMs) are used to organize the chemosensitivity data. Student's t-tests are used to identify SOM clusters with enhanced chemosensitivity for tumor cell lines with versus without genetically defective genes. Fisher's exact and chi-square tests are used to reveal instances where defective gene to chemosensitivity associations have enriched MOAs. The results of this analysis find a relatively small set of defective genes, inclusive of ABL1, AXL, BRAF, CDC25A, CDKN2A, IGF1R, KRAS, MECOM, MMP1, MYC, NOTCH1, NRAS, PIK3CG, PTK2, RPTOR, SPTBN1, STAT2, TNKS and ZHX2, as possible candidates for roles in chemosensitivity for compound MOAs that target primarily, but not exclusively, kinases, nucleic acid synthesis, protein synthesis, apoptosis and tubulin. These results find exploitable instances of enhanced chemosensitivity of compound MOA's for selected defective genes. Collectively these findings will advance the interpretation of pre-clinical screening data as well as contribute towards the goals of cancer drug discovery, development decision making, and explanation of drug mechanisms.

Relapse of anterior open bites treated with orthodontic appliances with and without orofacial myofunctional therapy.

INTRODUCTION: Closure and long-term retention of anterior open bites are significant concerns for orthodontists and their patients. In this study, we investigated the efficacy of orofacial myofunctional therapy (OMT) for maintaining closure of open bites in conjunction with orthodontic treatment. METHODS: The sample included 76 subjects with dental anterior open bites referred for OMT before, during, or after relapse of orthodontic treatment. The experimental cohort consisted of 27 subjects who received OMT and orthodontic treatment or retreatment. The control cohort comprised 49 subjects who had a history of orthodontic treatment with open-bite relapse. Overbite was evaluated by an OMT professional or orthodontist 2 months to 23 years after removal of the fixed appliances. Measurements were compared with t tests. RESULTS: Overbite relapse means were 0.5 mm (range, 0.0-4.0 mm) in the experimental group and 3.4 mm (range, 1.0-7.0 mm) in the control group, a difference that was clinically and statistically significant (P <0.0001). CONCLUSIONS: This study demonstrated that OMT in conjunction with orthodontic treatment was highly effective in maintaining closure of anterior open bites compared with orthodontic treatment alone.

Porcelain surface alterations and refinishing after use of two orthodontic bonding methods.

OBJECTIVE: To compare porcelain surfaces at debonding after use of two surface preparation methods and to evaluate a method for restoring the surface. MATERIALS AND METHODS: Lava Ceram feldspathic porcelain discs (n = 40) underwent one of two surface treatments prior to bonding orthodontic brackets. Half the discs had sandblasting, hydrofluoric acid, and silane (SB + HF + S), and the other half, phosphoric acid and silane (PA + S). Brackets were debonded using bracket removing pliers, and resin was removed with a 12-fluted carbide bur. The surface was refinished using a porcelain polishing kit, followed by diamond polishing paste. Measurements for surface roughness (Ra), gloss, and color were made before bonding (baseline), after debonding, and after each step of refinishing. Surfaces were also examined by scanning electron microscopy (SEM). Data was analyzed with 2-way ANOVA followed by Tukey HSD tests (alpha = 0.05). RESULTS: The SB + HF + S bonding method increased Ra (0.160 to 1.121 microm), decreased gloss (41.3 to 3.7) and altered color (DeltaE = 4.37; P < .001). The PA + S method increased Ra (0.173 to 0.341 microm; P < .001), but the increase in Ra was significantly less than that caused by the SB + HF + S bonding method (P < . 001). The PA + S method caused insignificant changes in gloss (41.7 to 38.0) and color (DeltaE = 0.50). The measurements and SEM observations showed that changes were fully restored to baseline with refinishing. CONCLUSIONS: The PA + S method caused significantly less damage to porcelain than the SB + HF + S method. The refinishing protocol fully restored the porcelain surfaces.

Outcome assessment of orthodontic clear aligner vs fixed appliance treatment in a teenage population with mild malocclusions.

OBJECTIVE: To assess the efficacy and efficiency of treatment in adolescents presenting with mild malocclusions, comparing outcomes using clear aligners to fixed appliances. MATERIALS AND METHODS: Patients identified retrospectively and consecutively from one private practice had been treated with either clear aligners (Invisalign, Align Technology, Santa Clara, Calif) or fixed appliances (0.022 Damon, Ormco, Orange, Calif; n = 26/group). Assessments of occlusion were made using the American Board of Orthodontics Discrepancy Index (DI) for initial records and Cast-Radiograph Evaluation (CRE) for final records. Number of appointments, number of emergency visits, and overall treatment time were determined from chart reviews. Data were analyzed using Pearson's correlation, Wilcoxon rank tests, unpaired t-tests, and Chi-square tests, with significance set to P ≤ .05. RESULTS: Pretreatment, the aligner and fixed groups showed no significant difference in overall severity (DI: 11.9 ± 5.3 vs 11.6 ± 4.8) or in any individual DI category. Posttreatment scores showed finishes for the aligner group had fewer discrepancies from ideal relative to the fixed appliance group (CRE: 30.1 ± 8.3 vs 37.0 ± 9.3; P < .01). Patients treated with aligners had fewer appointments (13.7 ± 4.4 vs 19.3 ± 3.6; P < .0001), fewer emergency visits (0.8 ± 1.0 vs 3.6 ± 2.5; P < .0001), and shorter overall treatment time (16.9 ± 5.7 vs 23.4 ± 4.4 months; P < .0001). CONCLUSIONS: Outcomes for treatment of mild malocclusions in adolescents showed equivalent effectiveness of clear aligners compared to fixed appliances, with significantly improved results for clear aligner treatment in terms of tooth alignment, occlusal relations, and overjet. Assessment of the number of appointments, number of emergency visits, and overall treatment time showed better outcomes for treatment with clear aligners.

Connecting chemosensitivity, gene expression and disease.

Omics-based investigations offer potentially powerful readouts that might be useful for probing the underlying biology of normal and diseased states, identifying novel therapeutic targets and proposing relevant markers for designing treatment strategies. A vital component of these investigations involves a systematic analysis of gene expression and chemosensitivity data in the context of disease states and small molecule probes into the function of targets responsible for a disease phenotype. Systematic analysis of chemical and pharmacogenetics data offers a possible means to identify novel, small-molecule, potentially therapeutic, agents that affect the phenotype of a particular target. Elegantly simple in concept, the covariation of genetic and chemosensitivity readouts provide a hypothetical link for relating compounds through genomic expression profiles to underlying biology.

Plaque retention by self-ligating vs elastomeric orthodontic brackets: quantitative comparison of oral bacteria and detection with adenosine triphosphate-driven bioluminescence.

INTRODUCTION: Enamel decalcification is a common problem in orthodontics. The objectives of this randomized clinical study were to enumerate and compare plaque bacteria surrounding 2 bracket types, self-ligating (SL) vs elastomeric ligating (E), and to determine whether adenosine triphosphate (ATP)-driven bioluminescence could be used for rapid assessment of bacterial load in plaque. METHODS: Patients (ages, 11-17 years) were bonded with SL and E brackets in 14 maxillary and 12 mandibular arches by using a split-mouth design. Recall visits were at 1 and 5 weeks after bonding. Plaque specimens were assayed for oral bacteria and subjected to ATP-driven bioluminescence determinations with a luciferin-based assay. RESULTS: In most patients, teeth bonded with SL attachments had fewer bacteria in plaque than did teeth bonded with E brackets. At 1 and 5 weeks after bonding, the means for SL vs E brackets were statistically lower for total bacteria and oral streptococci (P <0.05). ATP bioluminescence values were statistically correlated to the total oral bacteria and oral streptococci, with correlation coefficients of 0.895 and 0.843, respectively. CONCLUSIONS: SL appliances promote reduced retention of oral bacteria, and ATP bioluminescence might be a useful tool in the rapid quantification of bacterial load and the assessment of oral hygiene during orthodontic treatment.

Enantioselective synthesis of (+)-chamaecypanone C: a novel microtubule inhibitor.

A bicycle built for tubulin: The total synthesis of (+)-chamaecypanone C has been achieved by using a tandem retro-Diels-Alder/Diels-Alder cascade reaction (see scheme). Initial biological studies demonstrate that (+)-chamaecypanone C is an inhibitor of tubulin assembly and binds at the colchicine site.