The Development of Third-Generation Tetracycline Antibiotics and New Perspectives

Abstract

The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure. The first modern tetracycline introduced into therapy was tigecycline, followed by omadacycline, eravacycline, and sarecycline (the third generation). Structural and physicochemical key elements which led to the discovery of modern tetracyclines are approached. Thus, several chemical subgroups are distinguished, such as glycylcyclines, aminomethylcyclines, and fluorocyclines, which have excellent development potential. The antibacterial spectrum comprises several resistant bacteria, including those resistant to old tetracyclines. Sarecycline, a narrow-spectrum tetracycline, is notable for being very effective against Cutinebacterium acnes. The mechanism of antibacterial action from the perspective of the new compound is approached. Several severe bacterial infections are treated with tigecycline, omadacycline, and eravacycline (with parenteral or oral formulations). In addition, sarecycline is very useful in treating acne vulgaris. Tetracyclines also have other non-antibiotic properties that require in-depth studies, such as the anti-inflammatory effect effect of sarecycline. The main side effects of modern tetracyclines are described in accordance with published clinical studies. Undoubtedly, this class of antibiotics continues to arouse the interest of researchers. As a result, new derivatives are developed and studied primarily for the antibiotic effect and other biological effects.

Sarecycline Demonstrates Clinical Effectiveness against Staphylococcal Infections and Inflammatory Dermatoses: Evidence for Improving Antibiotic Stewardship in Dermatology

“…Several in vitro and mouse model studies showed sarecycline preferentially works against clinically relevant Gram-positive bacteria over Gram-negative bacteria [ 29 , 30 , 31 ]. This narrow-spectrum activity is the consequence of a focused design effort to make sarecycline more selective for the Gram-positive bacterium C. acnes [ 32 ], providing dermatologists a means to improve antibiotic stewardship in acne vulgaris therapy. Against 55 clinical isolates of C. acnes , sarecycline had a minimum inhibitory concentration (MIC) ranging from 0.5 to 16 µg/mL [ 31 ].…”

Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections

“…CaP-based bone-targeting therapies, including tetracycline, hydroxyapatite and bisphosphonates, have a high affinity for skeletal tissues and increase the topical concentration ( Figure 4 ). Tetracycline (TC) and its derivatives are an important class of broad-spectrum antibiotics ( Shi et al, 2020 ; Rusu and Buta, 2021 ). The tetracyclic naphthacene carboxamide ring is a basic structure.…”

The Role of Grass Compost and Zea Mays in Alleviating Toxic Effects of Tetracycline on the Soil Bacteria Community

“…Tetracyclines (Tc) represent a group of antibiotics with a broad spectrum of activities [ 1 , 2 ]. The first antibiotics from the class of tetracyclines (chlorotetracycline and oxytetracycline) were discovered at the end of 1940 s, with ultimately over 20 tetracyclines in use today [ 3 ].…”

“…The first antibiotics from the class of tetracyclines (chlorotetracycline and oxytetracycline) were discovered at the end of 1940 s, with ultimately over 20 tetracyclines in use today [ 3 ]. They can be divided into three categories: I generation tetracyclines (chlorotetracycline, oxytetracycline, tetracycline, demeclocycline), II generation tetracyclines (doxycycline, minocycline, lymecycline, meclocycline, metacycline, rolitetracycline), and III generation ones (tigecycline, omadacycline, sarecycline) [ 2 , 4 ]. The I generation antibiotics are naturally synthesized, whereas the II and III generation ones are semi-synthetic.…”