Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability

Guimarães, Daniel Silqueira Martins; Luz, Letícia Silveira de Sousa; Nascimento, Sara Batista do; Silva, Lorena Rabelo; Martins, Natália Rezende de Miranda; Almeida, Heloísa Gonçalves de; Reis, Vitória de Souza; Maluf, Sarah El Chamy; Budu, Alexandre; Marinho, Juliane Aparecida; Abramo, Clarice; Carmona, Adriana K.; Silva, Marina Goulart da; Silva, Gisele Rodrigues da; Kemmer, Victor Matheus; Butera, Anna Paola; Ribeiro-Viana, Renato; Gazarini, Marcos L.; Júnior, Clébio Soares Nascimento; Guimarães, Luciana; Santos, Fábio V.; Castro, Whocely Victor de; Viana, Gustavo Henrique Ribeiro; Brito, Cristiana Ferreira Alves de; Varotti, Fernando de Pilla

doi:10.1016/j.ejps.2019.105015

Cited by 12 publications

(16 citation statements)

References 47 publications

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“…The molecule 88 was evaluated against Plasmodium falciparum and shown to be more effective than its antecedent (IC 50 values of 1.55 and 14.7 µM, respectively). As it is a single molecule, the activity may be associated with the presence of a thio-linked long-chain hydrocarbon attached to the thiazole ring [125]. A new series of pyrazole-linked thiazole analogues was prepared.…”

Section: Thiazoles As Antimalarial Agentsmentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

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For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor–acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

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Section: Thiazoles As Antimalarial Agentsmentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

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“…A previous experiment from this research group indicated a purity of 99% using this route [ 53 ]. A related study carried out by Guimarães et al [ 54 ] reported the chemical synthesis 10-((4,5-dihydrothiazol-2-yl)thio)decan-1-ol ( Figure 7 B; compound 35 ). These authors produced this synthetic compound using a two-step reaction.…”

Section: Chemical Modification and Synthesis Of Marine Alkaloidsmentioning

confidence: 99%

“… Schematic representation of FBA-TPQ ( 5 ) ( A ) and 10-((4,5-dihydrothiazol-2-yl)thio)decan-1-ol ( 35 ) ( B ) syntheses (according to Wang et al [ 53 ] and Guimarães et al [ 54 ], respectively). …”

Section: Figurementioning

confidence: 99%

Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis

Munekata¹,

Pateiro²,

Conté-Júnior

et al. 2021

Marine Drugs

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Marine alkaloids comprise a class of compounds with several nitrogenated structures that can be explored as potential natural bioactive compounds. The scientific interest in these compounds has been increasing in the last decades, and many studies have been published elucidating their chemical structure and biological effects in vitro. Following this trend, the number of in vivo studies reporting the health-related properties of marine alkaloids has been increasing and providing more information about the effects in complex organisms. Experiments with animals, especially mice and zebrafish, are revealing the potential health benefits against cancer development, cardiovascular diseases, seizures, Alzheimer’s disease, mental health disorders, inflammatory diseases, osteoporosis, cystic fibrosis, oxidative stress, human parasites, and microbial infections in vivo. Although major efforts are still necessary to increase the knowledge, especially about the translation value of the information obtained from in vivo experiments to clinical trials, marine alkaloids are promising candidates for further experiments in drug development.

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“…The receptor is selected based on the pharmacological effect of interest, such as antiviral, anticancer, antibiotics, antifungal, antitubercular, antimalarial, etc. Preclinical tests can be negatively affected by the designing of drug candidates without adequate knowledge of the mode of action upon the probable targets [12]. One of the protein targets in Plasmodium falciparum is the adenylosuccinate lyase (PfADSL), an essential enzyme in purine metabolism in P. falciparum [13].…”

Section: Introductionmentioning

confidence: 99%

Molecular docking studies of Amidoxime-containing heterocyclic compounds from Zinc database against homology modelled PfADSL

Oduselu,

Ajani,

Adebiyi

2022

IOP Conf. Ser.: Earth Environ. Sci.

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Malaria remains one of the most infectious life-threatening diseases in the world. The lingering effect of drug resistance by malarial parasites, especially Plasmodium falciparum, has made it essential for the continuous search for novel antimalarial drugs that can act on new protein targets and through new modes of action. Amidoxime functional groups have, in recent years, shown to be good incorporations in heterocyclic backbones due to their vast biological activities. Hence, the antimalarial activities of some amidoxime-containing heterocyclic compounds have been predicted using molecular docking studies to determine the binding affinities and the inhibition constants of the compounds. The amidoxime-containing compounds were downloaded from the ZINC database and docked, using Auto Dock vina, against the active sites of homology modelled Plasmodium falciparumadenylosuccinate lyase (PfADSL) as obtained from the SWISS-MoDeL. The grid box was constructed using 80, 80, and 80, pointing in x, y, and z directions, respectively, with a grid point spacing of 0.375 A. The post-docking analysis, which entails determining the hydrogen bond formed and the bond length between the compounds and the protein target, was carried out using AutoDockTools, LigPlot and PyMOLmolecular viewer. The docking studies showed that the compounds possess binding affinities ranging from -8.6 to- 5.7 kcal/mol, with ZINC2268942 having the lowest binding affinity. The presence of the amidoxime-functional group on the best hit contributed significantly to the hydrogen bonds formed between the compound and the binding sites of PfADSL,which were observed atThr 124D, Ser 125D, Thr 172C, His 173C, Gln 250D, and Ser 299A. The results obtained from the molecular docking studies will be helpful in the development of a potential antimalarial drug that can target PfADSL after careful experimental validation of the target, then in vitro and in vivo screening.

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Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability

Cited by 12 publications

References 47 publications

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis

Molecular docking studies of Amidoxime-containing heterocyclic compounds from Zinc database against homology modelled PfADSL

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