Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

Abstract

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs ( 1–9 ) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9 , highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

N-Methyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-ylidene}hydrazinecarbothioamide

“…It is important to highlight that the substituents at the terminal N atom are relevant not only to the crystal packing, but also to the biological properties of the thiosemicarbazone derivatives. For example, a small chemical library of 4-methylthiosemicarbazones has been studied for the treatment of Parkinson's disease (Mathew et al, 2021) and for microbial growth inhibition (D'Agostino et al, 2022). In addition, for a review article on coordination compounds with 4-methylthiosemicarbazone derivatives including biological applications and catalytic activity, see: Monsur Showkot Hossain et al (2023).…”

Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates

“…Inhibitors of these enzymes have been clinically exploited for decades, and the discovery of multiple human isoforms [ 13 , 14 , 15 , 16 , 17 , 18 ] has led to many new applications and the development of new therapeutic principles, among them antiglaucoma [ 19 , 20 , 21 ] and antitumor drugs but also antiepileptic [ 22 , 23 , 24 , 25 , 26 ] and antiobesity drugs [ 27 , 28 , 29 ] as well as agents for the management of Alzheimer’s disease [ 30 , 31 ], neuropathic pain, cerebral ischemia, and some forms of arthritis [ 32 , 33 , 34 ]. Furthermore, the development of inhibitors for bacterial carbonic anhydrases is thought as a new concept to develop antibacterial drugs [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. In addition, drug conjugates were investigated for their ability to treat a variety of disorders in a multitargeting approach [ 43 , 44 , 45 , 46 , 47 ].…”

A new thiosemicarbazone and its 3d metal complexes: Synthetic, structural, and antioxidant studies

“…Thiosemicarbazones are the subject of constant and multidisciplinary interest, not only because of their structural features and extremely rich coordination chemistry, but also due to their versatile pharmacological properties such as antimicrobial, 1,2 antiviral, 3,4 anticonvulsant, 5,6 and carcinostatic activity. 7 Particular attention has been paid to thiosemicarbazones derived from N -heterocycles with α-carbonyl groups.…”