ABSTRACT
Hybrid-based drugs linked through a transition metal constitute an emerging concept for Plasmodium intervention. To advance the drug design concept and enhance the therapeutic potential of this class of drugs, we developed a novel hybrid composed of quinolinic ligands amodiaquine (AQ) and primaquine (PQ) linked by gold(I), named [AuAQPQ]PF6. This compound demonstrated potent and efficacious antiplasmodial activity against multiple stages of the Plasmodium life cycle. The source of this activity was thoroughly investigated by comparing parasite susceptibility to the hybrid's components, the annotation of structure-activity relationships and studies of the mechanism of action. The activity of [AuAQPQ]PF6 for the parasite's asexual blood stages was influenced by the presence of AQ, while its activity against gametocytes and pre-erythrocytic parasites was influenced by both quinolinic components. Moreover, the coordination of ligands to gold(I) was found to be essential for the enhancement of potency, as suggested by the observation that a combination of quinolinic ligands does not reproduce the antimalarial potency and efficacy as observed for the metallic hybrid. Our results indicate that this gold(I) hybrid compound presents a dual mechanism of action by inhibiting the beta-hematin formation and enzymatic activity of thioredoxin reductases. Overall, our findings support the potential of transition metals as a dual chemical linker and an antiplasmodial payload for the development of hybrid-based drugs.
ABSTRACT
BACKGROUND: Geographically isolated Hispanic populations, such as those living in Puerto Rico, may face unique barriers to health information access. However, little is known about health information access and health information-seeking behaviors of this population. OBJECTIVE: To examine differences in health and cancer information seeking among survey respondents who ever used the Internet and those who did not, and to explore sociodemographic and geographic trends. METHODS: Data for our analyses were from a special implementation of the Health Information National Trends Survey conducted in Puerto Rico in 2009. We collected data through random digit dialing, computer-assisted telephone interviews (N = 639). The sample was drawn from the eight geographic regions of the Puerto Rico Department of Health. To account for complex survey design and perform weighted analyses to obtain population estimates, we analyzed the data using SUDAAN. Frequencies, cross-tabulation with chi-square, and logistic regression analyses were conducted. Geographic information system maps were developed to examine geographic distributions of Internet use and information seeking. RESULTS: Of 639 participants, 142 (weighted percentage 32.7%) indicated that they had ever gone online to access the Internet or World Wide Web; this proportion was substantially lower than that of US mainland Hispanics who reported using the Internet (49%). While 101 of 142 (weighted percentage 59.6%) respondents who used the Web had ever sought health information, only 118 of 497 (weighted percentage 20.0%) of those who did not use the Web had sought health information. The pattern was similar for cancer information: 76 of 142 respondents (weighted percentage 47.2%) who used the Web had ever sought cancer information compared with 105 of 497 (weighted percentage 18.8%) of those who had not used the Web. These results were slightly lower but generally consistent with US mainland Hispanics' health (50.9%) and cancer (26.4%) information seeking. Results of separate logistic regression models controlling for sociodemographic characteristics demonstrated that, compared with individuals who did not seek health or cancer information, those who did were over 5 times as likely to have used the Internet (odds ratio 5.11, P < .001). Those who sought cancer information were over twice as likely to have used the Internet (odds ratio 2.5, P < .05). The frequency of Internet use and health and cancer information seeking was higher in the San Juan metro region than in more rural areas. CONCLUSIONS: Our results contribute to the evidence base for health and cancer communication planning for Puerto Rico, and suggest that health education and outreach efforts should explore the use of available and trusted methods of dissemination such as radio and television, as well as community-based health care providers and organizations, to supplement and encourage use of the Internet as a source of health information.