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Prof. Dr. Arthur D. Tinoco

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Department of Chemistry, University of Puerto Rico, Río Piedras Campus, Río Piedras, PR 00931, USA
Interests: bioinorganic chemistry; metal transport and regulation; metals in medicine

Special Issue Information

Dear Colleagues,

A recent study reported in the Lancet medical journal [1] has helped to contextualize the severity of the global impact of the growth of antibiotic-resistant superbugs. These bacterial infections are a leading cause of death, estimated to be directly attributable to 1.27 million deaths and associated with 4.95 million deaths in 2019. More than ever, the arsenal of drugs to combat these superbugs needs to be fortified in a very coordinated, worldwide effort. Research that focuses on exploiting the distinctive chemistry of transition metals or that which perturbs the essential metal homeostasis within pathogenic bacteria offers new avenues for antibiotic drug development. This Special Issue, titled “Weaponizing Metals Against Pathogenic Bacterial Superbugs”, is a collaboration between myself and the doctoral chemistry student Yazmary Meléndez-Contés. It aims to shed light on metal-centered antibacterial drug strategies that can specifically target pathogenic bacteria while minimizing cytotoxicity. Topics of interest include:

Combination treatments with metals and classical drugs or drug derivatives;
Development of metal-based complexes that introduce new modes of action;
Development of therapeutic approaches that offset the homeostasis of essential metals.

Reference

Murray, C.J.L.; Ikuta, K.S.; Sharara, F.; Swetschinski, L.; Robles Aguilar, G.; Gray, A.; Han, C.; Bisignano, C.; Rao, P.; Wool, E., et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. The Lancet doi:10.1016/S0140-6736(21)02724-0.

Prof. Dr. Arthur D. Tinoco
Guest Editor

Manuscript Submission Information

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Keywords

medicinal inorganic chemistry
drug discovery and development
bacterial superbugs
metal complexes
mechanism of antibacterial activity
antimicrobial activity
combinatorial treatment strategies
metal homeostasis

Published Papers (2 papers)

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Research

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10 pages, 3667 KiB

Open AccessArticle

Nanostructured γ-Al₂O₃ Synthesis Using an Arc Discharge Method and its Application as an Antibacterial Agent against XDR Bacteria

by Awatif Rashed Z. Almotairy, A. M. Amer, Hadir El-Kady, Bassma H. Elwakil, Mostafa El-Khatib and Ahmed M. Eldrieny

Inorganics 2023, 11(1), 42; https://doi.org/10.3390/inorganics11010042 - 15 Jan 2023

Cited by 5 | Viewed by 1694

Abstract

In the last few years, many efforts have been devoted to investigating the antibacterial activity of metal nanoparticles, especially against multidrug-resistant bacteria. Recently extensively drug-resistant (XDR) bacteria have emerged and caused a global threat. The purpose of this manuscript was to synthesize nanostructured γ-Al₂O₃ as an antibacterial agent against some XDRs. The results showed that Al₂O₃ was a mix of rod and spherical shapes in the nano range with diameters of less than 30 nm. The zeta potential was determined to estimate the surface charge for the synthesized γ-Al₂O₃, which was recorded as −34 ± 1.8 mV, indicating good stability. The synthesized nanostructured γ-Al₂O₃ showed a potent antibacterial activity against extensively drug-resistant Acinetobacter baumanii, with an inhibition zone diameter that reached 19 mm and a minimum inhibitory concentration (MIC) value that reached 2 µg/mL. The observed antibacterial activity of the prepared Al₂O₃ nanoparticles confirmed that the main mechanistic actions include bacterial cells apoptosis, ROS increment, cellular membrane disruption, and DNA damage. The cytotoxic effect (CC50) of the prepared γ-Al₂O₃-NPs was 1250 µg/mL in a normal human lung fibroblast cell line (WI-38 cells). It can be concluded that the synthesized γ-Al₂O₃ had an acceptable toxicity, which may pave the way for its use as a potent agent in the fight against XDR bacteria. Full article

(This article belongs to the Special Issue Weaponizing Metals against Pathogenic Bacterial Superbugs)

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Review

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23 pages, 3950 KiB

Open AccessReview

Copper-Based Antibiotic Strategies: Exploring Applications in the Hospital Setting and the Targeting of Cu Regulatory Pathways and Current Drug Design Trends

by Aixa M. Orta-Rivera, Yazmary Meléndez-Contés, Nataniel Medina-Berríos, Adriana M. Gómez-Cardona, Andrés Ramos-Rodríguez, Claudia Cruz-Santiago, Christian González-Dumeng, Janangelis López, Jansteven Escribano, Jared J. Rivera-Otero, Josean Díaz-Rivera, Sebastián C. Díaz-Vélez, Zulemaría Feliciano-Delgado and Arthur D. Tinoco

Inorganics 2023, 11(6), 252; https://doi.org/10.3390/inorganics11060252 - 8 Jun 2023

Cited by 1 | Viewed by 2122

Abstract

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs. Full article

(This article belongs to the Special Issue Weaponizing Metals against Pathogenic Bacterial Superbugs)

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