Evaluating Curriculum Differences in US PharmD Programs: A Peer Evaluation.

OBJECTIVE: To evaluate the differences in curriculum structure and content and observe commonalities across various Doctor of Pharmacy (PharmD) programs in the United States. METHODS: This research involves the collection of course content and credit hour data from the curricula and course descriptions, course catalogs, and student handbooks of all the PharmD programs available on their websites and categorization based on the content areas outlined in the Accreditation Council of Pharmacy Education. The core courses, elective offerings, and experiential education (eg, Introductory and Advanced Pharmacy Practice Experience) were evaluated using Excel® for credit hours, integration, non-integration, program duration (3-year vs 4-year), and online offerings. RESULTS: Of 142 accredited schools/colleges, 135 were included in the study, which met the inclusion criteria. In total, 85 of these schools have an integrated curriculum, 19 have a 3-year curriculum, and 15 offer a distance learning pathway for a PharmD degree. Fourteen of the 37 required content areas from the Accreditation Council of Pharmacy Education Appendix 1 were identified, with more than 50% of schools listing no credit hours allocated. Only 9 areas had 90% or more of pharmacy schools allocating credit hours. On average, biomedical, pharmaceutical, social/administrative/behavioral, clinical sciences, experiential education, and electives allocate 10.6, 25.3, 17.1, 40.5, 45.5, and 7.0 credit hours, respectively. CONCLUSION: Each school's curriculum has a significant variation in credit hours, and there is an opportunity to simplify the curricular structure and content by reducing redundancy and increasing flexibility based on health care needs.

The Status of Students, Faculty, and Leadership Diversities in US Pharmacy Schools/Colleges.

OBJECTIVE: The purpose of this research is to address knowledge gaps on diversity in the United States (US) population, pharmacy students, faculty, and school/college leadership. METHOD: The population data were collected from the US Census Bureau. The pharmacy student and faculty data were collected from the American Association of Colleges of Pharmacy enrollment and faculty profiles to compute Diversity Indices (DIs). To delve further into observed DI values, different ratios were calculated by dividing the total number of people in a racial/ethnic group of a particular category (eg, students) by the total number of people in the same racial/ethnic group in a different category (eg, faculty). Two factors (ratios among racial groups and changes in ratios over time) ANOVA without replication was conducted using Excel. RESULTS: The students are the most diverse category (average DI = 69%), followed by the US population (average DI = 58%), faculty diversity (average DI = 54%), assistant/associate dean (average DI = 42%) and dean (average DI = 31%). The ratio analyses among student, faculty, and leadership categories reveal a disproportionately high representation of White individuals in faculty and leadership roles when compared to other racial groups, resulting in low DI values in these categories. CONCLUSION: A significant ratio difference was found among various racial groups each year. However, there was no significant change observed in ratios over time. The academic community must develop hiring practices that increase the DI values among faculty and leadership categories to reduce the gap and promote student success.

Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes.

Praziquantel (PZQ) is the only drug available for the treatment of schistosomiasis, and since its large-scale use might be associated with the onset of resistance, new antischistosomal drugs should be developed. A series of 26 synthetic tetraazamacrocyclic derivatives and their metal complexes were synthesized, characterized, and screened for antischistosomal activity by application of a phased screening program. The compounds were first screened against newly transformed schistosomula (NTS) of harvested Schistosoma mansoni cercariae, then against adult worms, and finally, in vivo using the mouse model of S. mansoni infection. At a concentration of 33 µM, incubation with a total of 12 compounds resulted in the mortality of NTS at the 62% to 100% level. Five of these showing 100% inhibition of viability of NTS at 10 µM were selected for further screening for determination of the 50 inhibitory concentrations (IC50s) against both NTS and adult worms. Against NTS, all 5 compounds showed IC50s comparable to the IC50 of the standard drug, PZQ (0.87 to 9.65 µM for the 5 compounds versus 2.20 µM for PZQ). Three of these, which are the bisquinoline derivative of cyclen and its Fe(2+) and Mn(2+) complexes, showed micromolar IC50s (1.62 µM, 1.34 µM, and 4.12 µM, respectively, versus 0.10 µM for PZQ) against adult worms. In vivo, the worm burden reductions were 12.3%, 88.4%, and 74.5%, respectively, at a single oral dose of 400 mg/kg of body weight. The Fe(2+) complex exhibited activity in vivo comparable to that of PZQ, pointing to the discovery of a novel drug lead for schistosomiasis.

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands.

Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn(2+) complex of this ligand was the most potent with IC50s of 0.127 and 0.157µM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn(2+). Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.

Medicinal chemistry and the pharmacy curriculum.

The origins and advancements of pharmacy, medicinal chemistry, and drug discovery are interwoven in nature. Medicinal chemistry provides pharmacy students with a thorough understanding of drug mechanisms of action, structure-activity relationships (SAR), acid-base and physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. A comprehensive understanding of the chemical basis of drug action equips pharmacy students with the ability to answer rationally the "why" and "how" questions related to drug action and it sets the pharmacist apart as the chemical expert among health care professionals. By imparting an exclusive knowledge base, medicinal chemistry plays a vital role in providing critical thinking and evidence-based problem-solving skills to pharmacy students, enabling them to make optimal patient-specific therapeutic decisions. This review highlights the parallel nature of the history of pharmacy and medicinal chemistry, as well as the key elements of medicinal chemistry and drug discovery that make it an indispensable component of the pharmacy curriculum.

Synthesis and antimalarial activities of cyclen 4-aminoquinoline analogs.

In an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and also to overcome resistance to antimalarial agents, we synthesized three cyclen (1,4,7,10-tetraazacyclododecane) analogs of chloroquine [a bisquinoline derivative, 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline HBr, and a 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline-Zn(2+) complex]. The bisquinoline displays the most potent in vitro and in vivo antimalarial activities. It displays 50% inhibitory concentrations (IC(50)s) of 7.5 nM against the D6 (chloroquine-sensitive) clone of Plasmodium falciparum and 19.2 nM against the W2 (chloroquine-resistant) clone, which are comparable to those of artemisinin (10.6 and 5.0 nM, respectively) and lower than those of chloroquine (10.7 and 87.2 nM, respectively), without any evidence of cytotoxicity to mammalian cells, indicating a high selectivity index (>1,333 against D6 clone and >521 against W2 clone). Potent antimalarial activities of the bisquinoline against chloroquine- and mefloquine-resistant strains of P. falciparum were also confirmed by in vitro [(3)H]hypoxanthine incorporation assay. The in vivo antimalarial activity of the bisquinoline, as determined in P. berghei-infected mice, is comparable to that of chloroquine (50% effective dose,

Synthesis of isoquinuclidine analogs of chloroquine: antimalarial and antileishmanial activity.

The isoquinuclidine (2-azabicyclo[2.2.2]octane) ring system may be viewed as a semi-rigid boat form of the piperidine ring and, when properly substituted, a scaffold for rigid analogs of biologically active ethanolamines and propanolamines. It is present in natural products (such as ibogaine and dioscorine) that display interesting pharmacological properties. In this study, we have expanded our continuing efforts to incorporate this ring system in numerous pharmacophores, by designing and synthesizing semirigid analogs of the antimalarial drug chloroquine. The analogs were tested in vitro against Plasmodium falciparum strains and Leishmania donovani promastigote cultures. Compounds 6 and 13 displayed potent antimalarial activity against both chloroquine-susceptible D6 and the -resistant W2 strains of P. falciparum. All analogs also demonstrated significant antileishmanial activity with compounds 6 and 13 again being the most potent. The fact that these compounds are active against both chloroquine-resistant and chloroquine-sensitive strains as well as leishmanial cells makes them promising candidates for drug development.