Publications by authors named "Fabio Arias"

6 Publications

  • Page 1 of 1

Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors.

Bioorg Med Chem 2021 Aug 28;44:116294. Epub 2021 Jun 28.

Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Spain. Electronic address:

In search of new Nitric Oxide Synthase (NOS) inhibitor agents, two isosteric series of derivatives with an imidamide scaffold (one of them with a hydroxyl group and the other with a carbonyl one) were synthesized and evaluated on inducible (iNOS) and neuronal (nNOS) isoforms. These compounds have been designed by combining a kynurenamine framework with an amidine moiety in order to improve selectivity for the inducible isoform. In general, the in vitro inhibitory assays exhibited better inhibition values on the iNOS isoform, being the N-(3-(2-amino-5-methoxyphenyl)-3-hydroxypropyl)-4-(trifluoromethyl)benzimidamide 4i the most active inhibitor with the highest iNOS selectivity, without inhibiting eNOS. Docking studies on the two most active compounds suggest a different binding mode on both isozymes, supporting the experimentally observed selectivity towards the inducible isoform. Physicochemical in silico studies suggest that these compounds possess good drug-likeness properties.
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http://dx.doi.org/10.1016/j.bmc.2021.116294DOI Listing
August 2021

Antiglioma Activity of Aryl and Amido-Aryl Acetamidine Derivatives Targeting iNOS: Synthesis and Biological Evaluation.

ACS Med Chem Lett 2020 Jul 19;11(7):1470-1475. Epub 2020 Jun 19.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 31-66100 Chieti, Italy.

Nitric oxide is an important inflammation mediator with a recognized role in the development of different cancers. Gliomas are primary tumors of the central nervous system with poor prognosis, and the expression of the inducible nitric oxide synthase correlates with the degree of malignancy, changes in vascular reactivity, and neo-angiogenesis. Therefore, targeting the nitric oxide biosynthesis appears as a potential strategy to impair glioma progression. In the present work a set of aryl and amido-aryl acetamidine derivatives were synthesized to obtain new potent and selective inducible nitric oxide synthase inhibitors with improved physicochemical parameters with respect to the previously published molecules. Compound emerged as the most promising inhibitor and was evaluated on C6 rat glioma cell line, showing antiproliferative effects and high selectivity over astrocytes.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357225PMC
July 2020

Laryngeal Myofibroblastic Tumor: A New Therapeutic Approach. A Case Report.

Ear Nose Throat J 2021 Sep 13;100(8):NP368-NP372. Epub 2020 Apr 13.

Ear, Nose and Throat Department, 58355Hospital Rafael Méndez, Lorca, Spain.

Myofibroblastic tumors are rare lesions which can affect any part of the body. Although benign, their mass effect causes symptoms that can become life-threatening. Supraglottic laryngeal involvement is extremely rare, with only 4 cases described in the English literature. Because the pathophysiology is unknown and the incidence is so low, there is no standardized therapeutic management, although for laryngeal tumors surgery has traditionally been the preferred initial option. Another less common option is intravenous and oral corticosteroid therapy, but this is usually reserved for myofibroblastic tumors in other head and neck sites that are more difficult to access surgically, or patients who cannot undergo surgery. These lesions have a very high tendency to recur, and morbidity rates are therefore also high. We present a case of supraglottic myofibroblastic tumor in which we elected high-dose corticosteroid therapy as the only form of treatment. With this new therapeutic approach, we avoided the undesirable effects of the usual type of surgery. At the 12-month follow-up, the patient is in complete remission.
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http://dx.doi.org/10.1177/0145561320918741DOI Listing
September 2021

Synthesis of Cyclosiphonodictyol A and Its Bis(sulfato).

J Org Chem 2020 03 21;85(5):3799-3805. Epub 2020 Feb 21.

Departamento de Quı́mica Orgánica, Facultad de Ciencias, Instituto de Biotecnologı́a, Universidad de Granada, 18071 Granada, Spain.

The first synthesis of the marine benzoxepane hydroquinone cyclosiphonodictyol A and its bis(sulfato) from commercial (+)-sclareolide is reported. The key steps of the synthetic sequence (11 steps, 46% global) are the nucleophilic attack of a hindered tertiary alkoxide, a ring-closing metathesis reaction, and the Diels-Alder cycloaddition of a dienol acetate.
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http://dx.doi.org/10.1021/acs.joc.9b03434DOI Listing
March 2020

Protecting-Group-Free Synthesis of Cassane-Type Furan Diterpenes via a Decarboxylative Dienone-Phenol Rearrangement.

Org Lett 2018 11 29;20(22):7007-7010. Epub 2018 Oct 29.

Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología , Universidad de Granada , 18071 Granada , Spain.

An expeditious route to obtaining cassane-type furan diterpenes starting from (+)-sclareolide, an inexpensive commercially available natural lactone, has been achieved by using a solvent-free Diels-Alder cycloaddition and an unprecedented decarboxylative dienone-phenol rearrangement as key steps. Its applicability is showcased by the first synthesis of (5α)-vouacapane-8(14),9(11)-diene. The synthesis, which requires no protecting group, is efficient and atom- and step-economical (10 steps, 20% global).
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http://dx.doi.org/10.1021/acs.orglett.8b02867DOI Listing
November 2018

Quinazolinones, Quinazolinthiones, and Quinazolinimines as Nitric Oxide Synthase Inhibitors: Synthetic Study and Biological Evaluation.

Arch Pharm (Weinheim) 2016 Aug 21;349(8):638-50. Epub 2016 Jun 21.

Facultad de Farmacia, Departamento de Química Farmacéutica y Orgánica, Universidad de Granada, Granada, Spain.

The synthesis of different compounds with a quinazolinone, quinazolinthione, or quinazolinimine skeleton and their in vitro biological evaluation as inhibitors of inducible and neuronal nitric oxide synthase (iNOS and nNOS) isoforms are described. These derivatives were obtained from substituted 2-aminobenzylamines, using diverse cyclization procedures. Furthermore, the diamines were synthesized by two routes: A conventional pathway and an efficient one-pot synthesis in a continuous-flow hydrogenator. The structures of these heterocycles were confirmed by (1) H and (13) C nuclear magnetic resonance and high-resolution mass spectroscopy data. The structure-activity relationships of the target molecules are discussed in terms of the effects of both the R radical and the X heteroatom in the 2-position. In general, the assayed compounds behave as better iNOS than nNOS inhibitors, with the quinazolinone 11e being the most active inhibitor of all tested compounds and the most iNOS/nNOS selective one.
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http://dx.doi.org/10.1002/ardp.201600020DOI Listing
August 2016
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