Novel Cytotoxic Sesquiterpene Coumarin Ethers and Sulfur-Containing Compounds from the Roots of Ferula turcica.

Six new sesquiterpene coumarin ethers, namely turcicanol A (1), turcicanol A acetate (2), turcicanol B (3), turcica ketone (4), 11'-dehydrokaratavicinol (5), and galbanaldehyde (6), and one new sulfur-containing compound, namely turcicasulphide (7), along with thirty-two known secondary metabolites were isolated from the root of the endemic species Ferula turcica Akalin, Miski, & Tuncay through a bioassay-guided isolation approach. The structures of the new compounds were elucidated by spectroscopic analysis and comparison with the literature. Cell growth inhibition of colon cancer cell lines (COLO205 and HCT116) and kidney cancer cell lines (UO31 and A498) was used to guide isolation. Seventeen of the compounds showed significant activity against the cell lines.

Scaffold hopping and optimisation of 3',4'-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H.

Bioisosteric replacement and scaffold hopping are powerful strategies in drug design useful for rationally modifying a hit compound towards novel lead therapeutic agents. Recently, we reported a series of thienopyrimidinones that compromise dynamics at the p66/p51 HIV-1 reverse transcriptase (RT)-associated Ribonuclease H (RNase H) dimer interface, thereby allosterically interrupting catalysis by altering the active site geometry. Although they exhibited good submicromolar activity, the isosteric replacement of the thiophene ring, a potential toxicophore, is warranted. Thus, in this article, the most active 2-(3,4-dihydroxyphenyl)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one 1 was selected as the hit scaffold and several isosteric substitutions of the thiophene ring were performed. A novel series of highly active RNase H allosteric quinazolinone inhibitors was thus obtained. To determine their target selectivity, they were tested against RT-associated RNA-dependent DNA polymerase (RDDP) and integrase (IN). Interestingly, none of the compounds were particularly active on (RDDP) but many displayed micromolar to submicromolar activity against IN.

Patient and prescriber perceptions of depression screening within a community pharmacy setting.

OBJECTIVES: To determine patient and prescriber perceptions of depression screening within the community pharmacy setting and to assess the best strategies for patient engagement and care coordination. DESIGN: Qualitative semistructured key informant interviews using the Consolidated Framework for Implementation Research as a theoretical framework. SETTING AND PARTICIPANTS: A community pharmacy in the metropolitan Piedmont region of North Carolina from February 2019 to May 2019. Prescriber and patient interviews were audio recorded, transcribed, and independently coded by 2 investigators. A qualitative analysis was completed, with a selection of supporting quotations for each theme. OUTCOME MEASURES: Qualitative analysis of prescriber and patient perceptions of depression screening provided in community pharmacies, strategies for patient engagement, and coordination of care for depression screenings. RESULTS: Twelve patients and 4 prescribers participated in the study. The patient perceptions were categorized into 3 key themes: (1) private and confidential screenings; (2) disparate views regarding the potential interventions that pharmacists could offer; and (3) mental health stigma concerns. The prescriber perceptions were categorized into 3 key themes: (1) support for expanded access to depression screenings provided in community pharmacies; (2) necessity of referral algorithms for transitions of care; and (3) communication of full screening results for positive and negative screens. A mutual theme was identified among patients and prescribers: the view that mental health care provided at a community pharmacy was influenced by an established relationship with a community pharmacist. CONCLUSION: This study describes patient and provider perceptions of depression screening within the community pharmacy setting. Prescribers were supportive of community pharmacists' ability to close the gaps in access to care for patients with mental health conditions, whereas patients had mixed feelings that may have been influenced by concerns of privacy, confidentiality, and stigma. This deeper understanding of prescriber and patient perceptions of how community pharmacies could expand access to depression screening may provide a roadmap for offering these interventions in community pharmacies.

Deguelins, Natural Product Modulators of NF1-Defective Astrocytoma Cell Growth Identified by High-Throughput Screening of Partially Purified Natural Product Extracts.

A high-throughput screening assay for modulators of Trp53/NF1 mutant astrocytoma cell growth was adapted for use with natural product extracts and applied to a novel collection of prefractionated/partially purified extracts. Screening 68 427 samples identified active fractions from 95 unique extracts, including the terrestrial plant Millettia ichthyotona. Only three of these extracts showed activity in the crude extract form, thus demonstrating the utility of a partial purification approach for natural product screening. The NF1 screening assay was used to guide purification of active compounds from the M. ichthyotona extract, which yielded the two rotenones deguelin (1) and dehydrodeguelin (2). The deguelins have been reported to affect growth of a number of cancer cell lines. They potently inhibited growth of only one of a panel of NF1/Trp53 mutant murine astrocytoma cell lines, possibly related to epigenetic factors, but had no effect on the growth of normal astrocytes. These results suggest the potential utility of deguelins as tools for further investigating NF1 astrocytoma cell growth. These bioprobes were identified only as a result of screening partially purified natural product extracts.

Stellettapeptins A and B, HIV-inhibitory cyclic depsipeptides from the marine sponge Stelletta sp.

Two new HIV-inhibitory depsipeptides, stellettapeptins A (1) and B (2), were isolated from an extract of the marine sponge Stelletta sp., collected from northwestern Australia. Structures of these cyclic nonribosomal peptides were elucidated on the basis of extensive NMR data analysis, and chemical degradation and derivatization studies. Stellettapeptins contain numerous nonproteinogenic amino acid residues and they are the first peptides reported to contain a 3-hydroxy-6,8-dimethylnon-4-(Z)-enoic acid moiety. Compounds 1 and 2 potently inhibit infection of human T-lymphoblastoid cells by HIV-1RF with EC50 values of 23 and 27 nM, respectively.

A therapeutic lifestyle changes elective and its impact on student knowledge, empathy, and perceptions.

BACKGROUND AND PURPOSE: Engaging in therapeutic lifestyle changes (TLC) such as healthy eating and physical activity can help prevent or manage various conditions. This study's purpose is to describe a TLC elective course and examine its impact on student knowledge, empathy, and perceptions of confidence with lifestyle modifications counseling. EDUCATIONAL ACTIVITY AND SETTING: An elective was developed to increase student pharmacists' knowledge and confidence in educating patients about lifestyle modifications. Activities were intended to foster student empathy. A questionnaire, given at course initiation and conclusion, incorporated a knowledge quiz and Kiersma-Chen Empathy Scale (KCES). Student perceptions of confidence were assessed at course conclusion. FINDINGS: Knowledge significantly increased (P < .001) from 54.1% at course initiation to 75% at course conclusion when comparing average quiz scores. Average KCES scores (out of 105 points) were 84.9 (n = 26) and 86 (n = 22) at course initiation and conclusion, respectively, showing no significant change in empathy scores (P = .01). For each course topic, most students reported being somewhat or very confident in their TLC counseling abilities at course conclusion. SUMMARY: An elective course significantly improved TLC knowledge and perceived confidence regarding TLC counseling was high at course conclusion. Although there was no significant change in KCES scores, including dedicated TLC instruction in pharmacy curricula can help students build knowledge and confidence in TLC counseling in preparation for pharmacy practice.

Utilizing Flip® as a platform to facilitate a group project in a socially distanced environment.

BACKGROUND AND PURPOSE: This study evaluated the perceived impact of using Flip (Microsoft Corp.) to facilitate a group project in a socially distanced environment. EDUCATIONAL ACTIVITY AND SETTING: Student groups were assigned a self-care scenario, and students independently traveled to local pharmacies to identify a pertinent nonprescription product. Students individually recorded a review of the product using Flip. Subsequently, students reviewed and replied to group member videos to compare products. Students worked as a group to develop consensus regarding the most appropriate product recommendation for their scenario. At semester end, students completed a questionnaire about their experiences using Flip for the project. FINDINGS: Sixty-eight students (91%) completed the perceptions questionnaire at course conclusion. Students found Flip enjoyable (68%) and easy to use (74%). The majority of students (82%) viewed all of their group members' Flip videos, and most (88%) agreed or strongly agreed Flip facilitated group work in a socially distanced environment. SUMMARY: Students overall perceived Flip as enjoyable and easy to use. Though utilization of Flip was initially due social distancing requirements, the positive student feedback encouraged continued use of this platform asynchronously. Flip provides a unique mechanism for facilitating group projects in multiple different environments.

Impact of two methods for assigning groups in a team-based learning self-care course.

INTRODUCTION: Studies have examined the impact of team formation strategies to performance on team assessments and perceptions of team dynamics. This study assessed the impact of intentional vs. randomized team formation strategies on a semester-long self-care pharmacotherapy course taught using team-based learning. METHODS: Students were intentionally assigned to teams in fall 2018 and randomized to teams in fall 2019. Performance on team readiness assessment tests (TRATs) was compared. Student perceptions regarding team dynamics were evaluated using a questionnaire. RESULTS: The were no significant differences in TRAT scores between the intentional (n = 91; average 99.8%) and randomized (n = 68; average 99.9%) cohorts (P = .33). Response rates for the student perception questionnaires for the intentional and randomized cohorts were 85.7% and 77.9%, respectively. No significant differences existed between cohorts for any questionnaire items. CONCLUSIONS: The type and number of criteria used to intentionally develop teams has varied across the literature and has generally failed to show significant differences in performance on team assessments regardless of team formation strategy. There have been varied findings with respect to the impact of team formation criteria on student perceptions related to team dynamics. In this study, intentionally assigning teams in a single semester-long course primarily using community pharmacy experience and significant relationships did not produce significant differences in team performance or student perceptions compared to randomization. For teams in a single semester course, randomization may be an efficient way of assigning students to teams without negatively impacting team performance or perceptions of team dynamics.

Impact of a third-year post-graduation preparation elective course.

Background Limited literature is available evaluating retrospective student perceptions of the utility of a postgraduate preparation elective at graduation and career onset and its impact on residency match rates. This project sought to explore the perceived usefulness of a third-year elective course from 2016 to 2019 on post-graduation preparation and to compare the match rate of students enrolled vs. not enrolled in the elective. Impact The majority of students pursuing residency programs (94%) perceived the elective course as helpful in navigating the postgraduate training process. Of the students pursuing other employment, 77.8% found the elective to be helpful in navigating the employment process. The top five activities identified as most useful included: cover letters, letters of intent, and thank you cards overview; curriculum vitae workshop; interviewing tips; mock interviews; and overview of postgraduate training opportunities. The match rate was not statistically different between those who completed the elective (60.7%) vs. all school graduates (64.7%) (P =.70). Recommendations Consideration should be given to the topics to be included in this type of elective course depending on the targeted audience. Additionally, it may be more beneficial to introduce these types of topics and activities to students earlier in their didactic career and integrate them into different parts of the curriculum. Discussion The post-graduation preparation elective course was perceived positively by students in terms of preparing for their postgraduate plans. Limitations and confounders make it difficult to determine the true impact of this type of elective on successful residency match rates.

Microwave-based reaction screening: tandem retro-Diels-Alder/Diels-Alder cycloadditions of o-quinol dimers.

We have accomplished a parallel screen of cycloaddition partners for o-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels-Alder/Diels-Alder cascades of o-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels-Alder cycloadditions of o-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor.

Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian plant Nothospondias staudtii.

A high throughput screen for inhibitors of the oncogenic transcription factor activator protein-1 (AP-1) was applied to the NCI repository of natural product extracts. The liphophilic extract of the plant Nothospondias staudtii (Simaroubaceae) displayed significant AP-1 inhibition. Bioassay-guided fractionation of the extract lead to a new quassinoid named nothospondin (1), and the known compound glaucarubinone (2). The structure of 1 was elucidated by spectroscopic methods. Compounds 1 and 2 showed potent, dose-dependent AP-1 inhibition at noncytotoxic concentrations.

Inhibitors of the oncogenic transcription factor AP-1 from Podocarpus latifolius.

An activator protein-1 (AP-1) based bioassay-guided phytochemical investigation on Podocarpus latifolius led to the isolation of three new sempervirol-type diterpenes, cycloinumakiol (1), inumakal (2), and inumakoic acid (3), along with three known norditerpenes (4-6). Compounds 4 and 6 were responsible for the observed bioactivity.

Grassypeptolides F and G, cyanobacterial peptides from Lyngbya majuscula.

Grassypeptolides F (1) and G (2), bis-thiazoline-containing cyclic depsipeptides with a rare ß-amino acid, extensive N-methylation, and a large number of d-amino acids, are reported from an extract of the Palauan cyanobacterium Lyngbya majuscula. Both 1 and 2 were found to have moderate inhibitory activity against the transcription factor AP-1 (IC50 = 5.2 and 6.0 µM, respectively).

A simulated patient experience in the self-care aisle utilizing Flipgrid as a platform for sharing nonprescription product information.

BACKGROUND AND PURPOSE: Students visiting local pharmacies can enhance their learning about nonprescription products while improving their understanding of the patient self-care experience. This study was designed to examine student perceptions of an activity utilizing Flipgrid to share a simulated patient experience in the nonprescription aisle. EDUCATIONAL ACTIVITY AND SETTING: Student groups traveled to local pharmacies to review available products pertaining to a self-care scenario. Students submitted brief video recordings with product recommendations and counseling points via the Flipgrid platform. Following the activity, students submitted brief reflections. At course conclusion, students completed a questionnaire regarding perceptions of Flipgrid. FINDINGS: Sixty-eight students completed the activity. Response rates were 91.2% for the project reflection and 79.4% for the Flipgrid questionnaire. In the reflections (n = 62), the majority of students (87.1%) found it easy or extremely easy to locate pertinent nonprescription products; no student found it extremely difficult. All except four students indicated the assignment helped develop empathy, and all except two indicated a greater likelihood to help a patient in the aisle. In the Flipgrid questionnaire (n = 54), most students found the platform enjoyable (74.1%) and easy to use (79.6%). SUMMARY: Students perceived that the project increased empathy for assisting patients with selection of nonprescription products. Students found the Flipgrid platform enjoyable and easy to use. This activity can be utilized to simulate a patient self-care experience, and the Flipgrid platform is a novel way to share information between student groups in pharmacy education.

Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica.

Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O-methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 microM.

Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine crinoids.

Five new naphthopyrones (1-5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4H-naphtho[2,3-b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether (6-11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with <60% inhibition of ABCG2-mediated transport as compared to the positive control fumitremorgin C. None of the linear naphthopyrones inhibited ABCG2-mediated efflux.

Flipped classroom versus a didactic method with active learning in a modified team-based learning self-care pharmacotherapy course.

BACKGROUND AND PURPOSE: To examine the educational outcomes comparing flipped classroom method versus a didactic method with active learning in two semesters of a modified team-based learning (TBL) self-care pharmacotherapy course and explore student-identified preferences for teaching modality. EDUCATIONAL ACTIVITY AND SETTING: Grade performance on readiness assurance processes, both individual (iRAP) and team (tRAP), and exam questions were compared in two semester-long course offerings. Additionally, students were surveyed pre- and post-course. FINDINGS: The mean iRAP scores were 81.9% for the didactic method and 80.7% for the flipped method (p = .092). The mean tRAP scores were 93.6% for both didactic and flipped methods (p = .979). Mean exam performance for content taught using didactic and flipped methods were 83.3% and 83.5%, respectively (p = .730). Pre-course respondents indicated the following preferences: didactic (27.7%), flipped (9%), combination (58.2%), no preference (5.1%). Post-course, 46.8% preferred didactic, 5.7% preferred flipped, and 47.5% preferred a combination. Respondents perceived the didactic method helped develop deeper understanding, stimulated greater interest, and improved retention; however, they felt the flipped method improved critical thinking and application. SUMMARY: There were no statistically significant differences in student outcomes comparing teaching methods while student preference for the flipped classroom decreased.

The use of a disease state simulation assignment increased students' empathy and comfort with diabetes nutrition counseling.

BACKGROUND AND PURPOSE: To determine if a disease state simulation assignment increases empathy, comfort, and knowledge in diabetes nutrition counseling. EDUCATIONAL ACTIVITY AND SETTING: One-hundred forty students completing ambulatory care experiential rotations over two academic years were invited to participate in the study. Students in the intervention group completed an empathy assignment, which involved developing and following a diet plan appropriate for a patient with diabetes followed by a reflection of their experiences. Students completed a pre- and post-intervention survey assessing empathy, comfort with counseling, and knowledge of diabetes nutrition. FINDINGS: Fifty-three students (31 in the intervention, 22 in the non-intervention group) completed the pre- and post-survey and provided informed consent. Empathy scores on the Kiersma Chen Empathy Scale (range 15-105) improved by 6.4 points in students in the intervention group compared to a decline of 1.2 in students in the non-intervention group (p = 0.045). Comfort in counseling on a diabetes diet, measured on a 10-point scale, increased significantly more in students completing the empathy assignment (4.7 vs 3.5; p = 0.044). Knowledge (0-100%) improved by 9.7% and 8.6% in the intervention and non-intervention groups, respectively (p = 0.859). DISCUSSION: Similar to other studies using disease state simulations, the findings of this study show increased confidence in counseling and empathy. Given that the assignment used in this study is more specific to nutrition counseling, its use may be most helpful in settings where pharmacists are responsible for diabetes nutrition counseling. SUMMARY: Implementation of a similar assignment could be considered for experiential rotations with nutrition counseling.

Traditional lecture versus jigsaw learning method for teaching Medication Therapy Management (MTM) core elements.

BACKGROUND AND PURPOSE: To determine if traditional didactic lecture or the jigsaw learning method is more effective to teach the medication therapy management (MTM) core elements in a first year pharmacy course. EDUCATIONAL ACTIVITY AND SETTING: Traditional didactic lecture and a pre-class reading assignment were used in the fall semester cohort, and the jigsaw method was used in the spring semester cohort. Jigsaw is a cooperative learning strategy requiring students to assume responsibility for learning, and subsequently teaching peers. The students were responsible for reading specific sections of the pre-class reading, and then teaching other students in small groups about their specific reading assignments. To assess potential differences, identical pre- and post-tests were administered before and after the MTM section. Additionally, grade performance on an in-class project and final exam questions were compared, and students were surveyed on perceptions of teaching method used. FINDINGS: A total of 45 and 43 students completed both the pre- and post-test in the fall and spring (96% and 93% response rate), respectively. Improvement in post-test scores favored the traditional method (p = 0.001). No statistical differences were noted between groups with grade performance on the in-class project and final exam questions. However, students favored the jigsaw method over traditional lecture and perceived improvements in problem solving skills, listening/communication skills and encouragement of cooperative learning (p = 0.018, 0.025 and 0.031). SUMMARY: Although students favored the jigsaw learning method, traditional didactic lecture was more effective for the pre- and post-knowledge test performance. This may indicate that traditional didactic lecture is more effective for more foundational content.

Reflections on a year-long student and pharmacist paired mentorship program.

BACKGROUND AND PURPOSE: Mentorship programs can play a significant role in the professional development of a variety of individuals, including student pharmacists and practitioners. Many mentorship programs have been described in the literature, but the literature pertaining to mentorship programs for student pharmacists specifically is varied. EDUCATIONAL ACTIVITY AND SETTING: A leadership society at one school of pharmacy established a formal mentorship program to aid the professional development of student pharmacists. This year-long program matched third-year student pharmacists with practicing pharmacists. This paper describes the development of the program, along with perceived benefits and challenges associated with implementation. FINDINGS: The mentor (n=8) and mentee (n=17) respondents provided positive feedback (100% and 94%, respectively) regarding the mentorship program. Most mentors and mentees noted they enjoyed having the opportunity to network and gained different perspectives on issues related to pharmacy. The challenges most noted by both the mentors and mentees were time limitations and scheduling conflicts. More consistent communication between mentors and mentees was noted as an area of improvement for future programs. DISCUSSION: The described program may create avenues to achieve professional development elements of the 2016 Accreditation Council for Pharmacy Education (ACPE) Standards and 2013 Center for Advancement of Pharmacy Education (CAPE) Outcomes. Continued, regular evaluation is important to help with process improvement, address challenges, and ensure the program is meeting desired objectives. Adjustments may be needed based on participant feedback, available resources, and student interest. SUMMARY: Overall, the program was successful, helping participants grow personally and professionally. With modifications, other institutions may utilize this data to develop similar programs.