antibiotics Review Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity—A Pharmaco-Toxicological Screening Daniel Florin Pancu 1,† , Alexandra Scurtu 2,3,† , Ioana Gabriela Macasoi 2,3, *, Daniela Marti 4, *, Marius Mioc 2,3 , Codruta Soica 2,3 , Dorina Coricovac 2,3 , Delia Horhat 1 , Marioara Poenaru 1 and Cristina Dehelean 2,3   Citation: Pancu, D.F.; Scurtu, A.; Macasoi, I.G.; Marti, D.; Mioc, M.; Soica, C.; Coricovac, D.; Horhat, D.; Poenaru, M.; Dehelean, C. Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity—A Pharmaco-Toxicological Screening. Antibiotics 2021, 10, 401. https://doi.org/10.3390/ antibiotics10040401 Academic Editor: Giulia Bernardini Received: 13 March 2021 Accepted: 31 March 2021 Published: 7 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Faculty of Medicine, “Victor Babes , ” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 1, 300041 Timisoara, Romania; pancudaniel87@gmail.com (D.F.P.); deliahorhat@yahoo.com (D.H.); marioara.poenaru@gmail.com (M.P.) 2 Faculty of Pharmacy, “Victor Babes , ” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; alexandra.scurtu@umft.ro (A.S.); marius.mioc@umft.ro (M.M.); codrutasoica@umft.ro (C.S.); dorinacoricovac@umft.ro (D.C.); cadehelean@umft.ro (C.D.) 3 Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania 4 Faculty of Medicine, Western University Vasile Goldis Arad, 94 Revolutiei Blvd., 310025 Arad, Romania * Correspondence: macasoi.ioana@umft.ro (I.G.M.); dana_m73@yahoo.com (D.M.) † These authors contributed equally to this work. Abstract: Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed. Keywords: antibiotics; toxicity; antibiotic resistance; classification; natural compounds; antitumor; mechanism of action 1. Introduction The discovery of antibiotics in a time when humankind was decimated by different infectious diseases represented a miraculous medical act. Since then, antibiotics have remained in the focus of researchers from different medical fields due to the multiple essen- tial roles played by these compounds in the fight against various pathogens that threaten human health. The development of resistant bacteria to almost all existent antibiotics has become a global threat and an issue of great concern. Moreover, the misuse and the overuse of antibiotics, together with antibiotic-related severe side effects, are clear signals for the imperative need to discover novel therapeutic approaches. The present manuscript provides a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the up-to-date classification and adverse effects associated with antibiotics therapy. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis, with using natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy being discussed. Antibiotics 2021, 10, 401. https://doi.org/10.3390/antibiotics10040401 https://www.mdpi.com/journal/antibiotics