Adelfa E Serrano PhD

University of Puerto Rico, Medical Sciences Campus · Department of Microbiology and Medical Zoology

Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Init...

The development of novel antiplasmodial compounds with broad-spectrum activity against different stages of Plasmodium parasites is crucial to prevent malaria disease and parasite transmission. This study evaluated the antiplasmodial activity of seven novel hydrazone compounds (referred to as CB compounds: CB-27, CB-41, CB-50, CB-53, CB-58, CB-59, a...

Purpose Antimalarial drug resistance is a global public health problem that leads to treatment failure. Synergistic drug combinations can improve treatment outcomes and delay the development of drug resistance. Here, we describe the implementation of a freely available computational tool, Machine Learning Synergy Predictor (MLSyPred©), to predict p...

Gracilioether M (6) and 11,12-dihydrogracilioether M (7), two polyketides with a [2(5H)-furanylidene]ethanoate moiety, along with known plakortone G (9) and its new naturally occurring derivative 9,10-dihydroplakortone G (8), were isolated from the Caribbean marine sponge Plakortis halichondrioides. The structures and absolute configuration of 6, 7...

Antimicrobial and antiviral resistances are worldwide public health threats, causing treatment failures and increasing morbidity and mortality. Mycobacterium tuberculosis and Plasmodium falciparum, among many others, are examples of multidrug-resistant pathogens requiring combinatorial drug therapy. The use of drug combinations acting in synergy re...

Plasmodium falciparum parasites are increasingly drug-resistant, requiring the search for novel antimalarials with distinct modes of action. Enzymes in the glutathione pathway, including glutathione S-transferase (GST), show promise as novel antimalarial targets. This study aims to better understand the biological function of Plasmodium GST, assess...

Endothelial abnormalities play a critical role in the pathogenesis of malaria caused by the human pathogen, Plasmodium falciparum. In serious infections and especially in cerebral malaria, red blood cells infected with the parasite are sequestered in small venules in various organs, resulting in endothelial activation and vascular occlusion, which...

This essay introduces a series of five historical articles on the scientific and educational contributions of the University of Puerto Rico School of Tropical Medicine (STM), under the auspices of Columbia University (1926-1949), to the fields of tropical medicine and public health. The articles will appear in several consecutive issues, and will a...

Plasmodium parasites are exposed to endogenous and exogenous oxidative stress during their complex life cycle. To minimize oxidative damage, the parasites use glutathione (GSH) and thioredoxin (Trx) as primary antioxidants. We previously showed that disruption of the Plasmodium berghei gamma-glutamylcysteine synthetase (pbggcs-ko) or the glutathion...

Multidrug resistance-associated proteins (MRP) belong to the C-family of ATP-binding cassette (ABC) transport proteins, and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. Rodent malaria parasites encode a single ABCC protein, whereas human parasites encode two: MRP1 an...

Malaria is one of the most devastating parasitic diseases worldwide. Plasmodium drug resistance remains a major challenge to malaria control and has led to the re-emergence of the disease. Chloroquine (CQ) and artemisinin (ART) are thought to exert their anti-malarial activity inducing cy-totoxicity in the parasite by blocking heme degradation (for...

Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure–activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. f...

Antimalarial drug development is of outmost importance to achieve malaria eradication, especially by targeting the blood stages critical to parasite development. Identification and validation of potential drug targets is required for the development of novel antimalarials. Glutathione S‐transferase (GST) is a detoxification enzyme that has been ass...

S-adenosyl-l-methionine decarboxylase (AdoMetDC) in the polyamine biosynthesis pathway has been identified as a suitable drug target in Plasmodium falciparum parasites, which causes the most lethal form of malaria. Derivatives of an irreversible inhibitor of this enzyme, 5′-{[(Z)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine (MDL73811), have bee...

Here we report the discovery of tetracyclic benzothiazepines (BTZs) as highly potent and selective antimalarials along with the identification of the Plasmodium falciparum cytochrome bc(1) complex as the primary functional target of this novel compound class. Investigation of the structure activity relationship within this previously unexplored che...

Flow cytometry is a potentially efficient approach for the quantification of parasitemias in experimental malaria infections and drug susceptibility assays using rodent malaria models such as Plasmodium berghei. In this study, we used two red DNA-binding fluorochromes, rhodamine 800 (R800) and LD700, to measure parasitemia levels in whole blood sam...

This study characterizes aminoindole molecules that are analogs of Genz-644442. Genz-644442 was identified as a hit in a screen of ~70,000 compounds in the Broad Institute's small-molecule library and the ICCB-L compound collection at Harvard Medical School. Genz-644442 is a potent inhibitor of Plasmodium falciparum in vitro (50% inhibitory concent...

Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high thr...

The development of a concise strategy to access 2-amino-3-hydroxy-indoles, which are disclosed as novel antimalarials with potent in vivo activity, is reported. Starting from isatins the target compounds are synthesized in 2 steps and in good yields via oxoindole intermediates by employing tert-butyldimethylsilyl amine (TBDMSNH(2)) as previously un...

Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a gamma-glutamylcysteine synthetase (gamma-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical...

Malaria is a global health problem caused by Plasmodium parasites. Glutathione S-transferase (GST) is involved in the conjugation of glutathione to drugs and toxic compounds. It is postulated that GST plays an important role in the development of drug resistance. The three-dimensional (3D) structure of Plasmodium falciparum GST (PfGST) has been sol...

[This corrects the article on p. e1000302 in vol. 5, PMID: 19229315.].

Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this...

The ATP-binding cassette (ABC) superfamily is one of the largest evolutionarily conserved families of proteins. ABC proteins play key roles in cellular detoxification of endobiotics and xenobiotics. Overexpression of certain ABC proteins, among them the multidrug resistance associated protein (MRP), contributes to drug resistance in organisms rangi...

Complete pbmrp nucleotide sequence and predicted amino acid sequence. The complete nucleotide sequence of the pbmrp gene from the Plasmodium berghei line is presented together with the predicted protein sequence.

Primers used in pbmrp sequencing reactions. Table that includes all the primer combinations used to sequence the pbmrp gene in the Plasmodium berghei N clone line. Forward and reverse primers are prefaced with an F or an R, respectively.

Complete multiple sequence alignment the MRP sequences from five Plasmodium species. The complete multiple sequence alignment for the MRPs obtained from five Plasmodium species: P. y. yoelii, P. berghei, P. vivax, P. knowlesi, and P. falciparum, is show.

The molecular mechanisms by which the malarial parasite has managed to develop resistance to many antimalarial drugs remain to be completely elucidated. Mutations in the pfmdr1 gene of Plasmodium falciparum, as well as an increase in pfmdr1 copy number, have been associated with resistance to the quinoline-containing antimalarial drugs. We investig...

The ATP-binding cassette (ABC) proteins are one of the largest evolutionarily conserved families. They are characterized by the presence of highly conserved nucleotide-binding sites (NBS). In the present study, we identified ABC genes in rodent Plasmodia. We queried the Plasmodium yoelii genome with the ABC signature motif and retrieved 15 contigs....

The rapid emergence of multidrug-resistant Plasmodium falciparum is a worldwide concern. Despite the magnitude of the problem, the mechanisms involved in this phenomenon are not well understood. One current proposal suggests that toxic heme molecules are degraded by glutathione (GSH), and that anti-malarial drugs, such as chloroquine (CQ), inhibit...

An evaluation of 3 different methods for malaria diagnosis was carried out in an urban area of low endemicity on the Pacific coast of Colombia. Samples were collected from 833 symptomatic patients at a malaria clinic and examined by the polymerase chain reaction (PCR), quantitative buffy coat (QBC; Becton Dickinson, Franklin Lakes, NJ) method, and...

Malaria is no longer endemic in Puerto Rico, however, imported cases of the disease are occasionally reported to the Health Department of the Island. This is a report of a 45-year-old female patient who traveled to Kenya and Niger and was admitted to a San Juan area hospital with an 8 day history of daily chills and fever, myalgia, nausea and vomit...

Amplification, mutations, or overexpression of the pfmdr1 gene have been associated with multiple drug resistance in some strains of Plasmodium falciparum. In order to better understand this potential mechanism of drug resistance, we are currently investigating putative mdr homologues in vivo in the rodent malaria Plasmodium berghei. We have identi...

Serrano, A. E., Robinson, B. L., Peters, W., and Trujillo-Nevárez, K. 1999.Plasmodium bergheiandPlasmodium yoelii:Molecular karyotypes of drug-resistant lines.Experimental Parasitology91,93–96.

The malaria parasite Plasmodium falciparum contains at least two genes related to the mammalian multiple drug resistance genes, and at least one of the P. falciparum genes is expressed at a higher level and is present in higher copy number in a strain that is resistant to multiple drugs than in a strain that is sensitive to the drugs.

A Fasciola hepatica tegument antigen preparation was obtained from intact adult worms by solubilization with a non-ionic detergent, Nonidet P-40. This antigen preparation contains antigens useful for the serodiagnosis of infection with this parasite. However, the antigen preparation is inadequate for use in the enzyme-linked immunosorbent assay (EL...

The presence of cross-reacting antigens between Paragonimus westermani, Schistosoma mansoni, and Fasciola hepatica adult worms was demonstrated by Ouchterlony immunodiffusion and enzyme-linked immunosorbent assay (ELISA). A serum bank was developed against the three trematode genera to serve as probes to determine the presence of cross-reacting ant...

Immunity to infection due to Schistosoma mansoni was induced in CBAI J mice by using a tegument antigen from Fasciola hepatica worms. Multiple immunizations resulted in up to 83% higher worm-burden reductions than did single immunizations. Th.e vaccine also had an adverse effect on the fecundity of female schistosome worms, whIch resulted in a lowe...

Typescript (Photocopy). Thesis (M.S.)--Universidad de Puerto Rico, 1981. Includes bibliographical references (leaves 91-97).