Design, synthesis, in vitro and in vivo trypanosomaticidal efficacy of novel 5-nitroindolylazines.

Leishmaniasis and trypanosomiasis rank among lethal vector-borne parasitic diseases that are endemic in tropical and sub-tropical countries. There are currently no preventive vaccines against them, and once diagnosed, a handful of less effective drugs clinically accessible are the only therapeutic options offered to treat these ailments. And although curable, the eradication and elimination of these diseases are hampered by the emergence of multidrug-resistant strains of the causal pathogens.

Investigation of Novel Isatinylhydantoin Derivatives as Potential Anti-Kinetoplastid Agents.

Neglected tropical diseases are a group of infectious diseases with a high endemicity in developing countries of Africa, Asia, and the Americas. Treatment for these diseases depends solely on chemotherapy, which is associated with severe side effects, toxicity, and the development of parasitic resistance. This highlights a critical need to develop new and effective drugs to curb these diseases.

Synthesis and In Vitro Antileishmanial Efficacy of Novel Ethylene Glycol Analogues of Benzothiadiazine-1,1-dioxide.

Leishmaniasis is a vector-borne, parasitic disease affecting millions of people and animals worldwide. Current therapeutic options have proven to be ineffective in both treating the disease and preventing its spread. As a result, new drugs must be developed to effectively combat this disease.

In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives.

African trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock's most virulent trypanosome species.

and Trypanocidal Efficacy of Nitrofuryl- and Nitrothienylazines.

African trypanosomiasis is a vector-borne disease of animals and humans in the tsetse fly belt of Africa. ("nagana") is the most pathogenic trypanosome in livestock and causes high morbidity and mortality rates among cattle. In the absence of effective preventative vaccines, the management of trypanosomiasis relies on chemoprophylaxis and/or -therapy.

Design, synthesis, electrochemistry and anti-trypanosomatid hit/lead identification of nitrofuranylazines.

Chagas disease and leishmaniasis are vector-borne infectious diseases affecting both humans and animals. These neglected tropical diseases can be fatal if not treated. Hundreds to thousands of new Chagas disease and leishmaniasis cases are being reported by the WHO every year, and currently available treatments are insufficient.

On the basis of sex: male vs. female rat adenosine A/A receptor affinity.

Objective: To ensure reproducibility in biomedical research, the biological variable sex must be reported; yet a reason for using male (instead of female) rodents is seldom given. In our search for novel adenosine receptor ligands, our research group routinely determines a test compound's binding affinities at male Sprague-Dawley rat (r) adenosine A and A receptors via in vitro radioligand binding studies. This pilot study compared the binding affinities of four adenosine receptor ligands (frequently used as reference standards) at male and female adenosine rA and rA receptors.

In vitro trypanocidal activities and structure-activity relationships of ciprofloxacin analogs.

Tropical diseases, such as African trypanosomiasis, by their nature and prevalence lack the necessary urgency regarding drug development, despite the increasing need for novel, structurally diverse antitrypanosomal drugs, using different mechanisms of action that would improve drug efficacy and safety. Traditionally antibacterial agents, the fluoroquinolones, reportedly possess in vitro trypanocidal activities against Trypanosoma brucei organisms. During our research, the fluroquinolone, ciprofloxacin (1), and its analogs (2-24) were tested against bloodstream forms of T.

Exploration of ethylene glycol linked nitrofurantoin derivatives against Leishmania: Synthesis and in vitro activity.

Leishmaniasis is a neglected tropical disease that is caused by the Leishmania parasite. It is estimated that there are more than 350 million people at risk of infection annually. Current treatments that are in clinical use are expensive, have toxic side effects, and are facing parasitic resistance.

Synthesis and in vitro antileishmanial activity of alkylene-linked nitrofurantoin-triazole hybrids.

Leishmaniasis is a vector-borne parasitic disease that mostly affects populations in tropical and sub-tropical countries. There is currently no protective anti-leishmanial vaccine and only a paucity of clinical drugs is available to treat this disease albeit their toxicity. Leishmaniasis is curable but its eradication and elimination have been hampered by the emergence of multidrug resistant strains of the causative pathogens.

Design, synthesis and evaluation of amino-3,5-dicyanopyridines and thieno[2,3-b]pyridines as ligands of adenosine A receptors for the potential treatment of epilepsy.

Due to the implication of adenosine in seizure suppression, adenosine-based therapies such as adenosine receptor (AR) agonists have been investigated. This study aimed at investigating thieno[2,3-]pyridine derivatives as non-nucleoside A agonists that could be used in pharmaco-resistant epilepsy (PRE). Compound (thieno[2,3-]pyridine derivative), displayed good binding affinity to the rA AR (  = 61.

Chalcone-inspired rA /A adenosine receptor ligands: Ring closure as an alternative to a reactive substructure.

Over the past few years, great progress has been made in the development of high-affinity adenosine A and/or A receptor antagonists-promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure-related concerns. The present study investigated the effect of ring closures on the rA /A affinity of compounds containing a highly reactive α,β-unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns.

New fused pyrroles with rA1/A2A antagonistic activity as potential therapeutics for neurodegenerative disorders.

In a pilot study, eleven pyrrolopyridine and pyrrolopyrimidine derivatives (specifically, 7-azaindole and 7-deazapurine derivatives) were synthesised by Suzuki cross-coupling reactions and evaluated via radioligand binding assays as potential adenosine receptor (AR) antagonists in order to further investigate the structure-activity relationships of these compounds. 6-Chloro-4-phenyl-1H-pyrrolo[2,3-b]pyridine, with a 7-azaindole scaffold, was identified as a selective A AR antagonist with a rAK value of 0.16 µM, and interestingly, the addition of a N-atom to the aforementioned fused heterocyclic ring system, creating corresponding 7-deazapurines, led to a dual A/A AR ligand (2-chloro-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine: rAK: 0.

Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.

Adenosine receptors (ARs) are ubiquitously distributed throughout the mammalian body where they are involved in an extensive list of physiological and pathological processes that scientists have only begun to decipher. Resultantly, AR agonists and antagonists have been the focus of multiple drug design and development programmes within the past few decades. Considered to be a privileged scaffold in medicinal chemistry, the chalcone framework has attracted a substantial amount of interest in this regard.

C3 amino-substituted chalcone derivative with selective adenosine A receptor affinity in the micromolar range.

Abstract: To identify novel adenosine receptor (AR) ligands based on the chalcone scaffold, herein the synthesis, characterization and in vitro and in silico evaluation of 33 chalcones (- and -) and structurally related compounds (-) are reported. These compounds were characterized by radioligand binding and GTP shift assays to determine the degree and type of binding affinity, respectively, against rat () A and A ARs. The chalcone derivatives , , and possessed selective A affinity below 10 µM, and thus, are the most active compounds of the present series; compound was the most potent selective A AR antagonist ( () = 1.

Synthesis and Structure Activity Relationships of Chalcone based Benzocycloalkanone Derivatives as Adenosine A1 and/or A2A Receptor Antagonists.

Adenosine A and/or A receptor antagonists hold promise for the potential treatment of neurological conditions, such as Parkinson's disease. Herein, a total of seventeen benzocycloalkanone derivatives were synthesised and evaluated for affinity towards adenosine receptors (A and A AR). The obtained results allowed for the conclusion that affinity and/or selectivity of the 2-benzylidene-1-indanone and -tetralone derivatives toward A and/or A ARs may be modulated by the nature of the substituents (either -OH, -OCH or morpholine) attached at position C4 of the 1-indanone core and C5 of the 1-tetralone core as well as the (C3') and/or (C4') position(s) on ring B.

Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A and/or A receptor antagonists.

A series of fourteen methoxy substituted 2-benzoyl-1-benzofuran derivatives were synthesised and their affinities determined for adenosine A and A receptors via radioligand binding assays to establish the structure activity relationships pertinent for A and A affinity. Compound 3j (6,7-dimethoxybenzofuran-2-yl)(3-methoxyphenyl)methanone exhibited A affinity (AK (rat) = 6.880 µM) as well as A affinity (AK (rat) = 0.

Methoxy substituted 2-benzylidene-1-indanone derivatives as A and/or A AR antagonists for the potential treatment of neurological conditions.

A prior study reported on hydroxy substituted 2-benzylidene-1-indanone derivatives as A and/or A antagonists for the potential treatment of neurological conditions. A lead compound () was identified with both A and A affinity in the micromolar range. The current study explored the structurally related methoxy substituted 2-benzylidene-1-indanone derivatives with various substitutions on ring A and B of the benzylidene indanone scaffold in order to enhance A and A affinity.