Salicylanilides and Their Derivates as Perspective Anti-tuberculosis Drugs: Synthetic Routes and Biological Evaluations

Abstract

Salicylanilides are a well-known family of pharmacological compounds, which are under renewed investigation because of the discovery of novel interesting biological activities and mechanisms of action over the last decade. This comprehensive mini-review describes the biological and pharmacological properties of salicylanilides, their activity against atypical and multi-drug resistant mycobacterial strains, and synthetic routes for their preparation. In particular, this review focuses on the synthesis and biological properties of salicylanilides and O-substituted derivates reported between 2000 and 2010, which have displayed the highest antituberculosis or antifungal activity.

Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenyl)carbamoyl]naphthalen-2-yl Carbamates

“…On the other hand, the blocking of the phenolic moiety by the carbamate group significantly increased the antimicrobial effect of these compounds. The mode of action (targets) of these compounds is questionable; however, due to the structural similarity with salicylanilides, interactions with vital enzymes, energy metabolism, as well as disturbing of the membrane architecture of prokaryotic cells may be supposed [10,11,13,14,15,16,17,32,33,36,44].…”

“…Salicylanilides have been described to affect a wide range of targets, although the appropriate mechanism of action responsible for overall biological activities of these compounds has not been proposed so far. Thus, salicylanilides seem to be promising candidates for antibacterial agents, which could be a solution to the resistance challenges [10,11,12,13,14,15,16,17].…”

Hybrids of Salicylalkylamides and Mannich Bases: Control of the Amide Conformation by Hydrogen Bonding in Solution and in the Solid State

“…Salicylic acid amides are privileged scaffolds in medicinal chemistry. Pharmacological activities have been reported for numerous N- aryl (anilides) and N- alkyl salicylamides in the fields of antimicrobials [1,2,3,4,5,6,7,8,9,10,11,12], antivirals [13,14,15,16,17], anthelmintics [18,19], antimalarials [20,21,22,23], antimycotics [24], molluscicides [25,26], as well as target-specific interactions [27,28,29,30,31,32,33]. The conformations of salicylamides in solution and in the solid state are controlled by inter- and intramolecular networks of different types of hydrogen bonding.…”

Crystal Structure of the 5-Chloro Salicylamides: Three Different Types of the H-bonding Influenced Linear Chain Formation in the Solid State

“…Other synthetic approaches were also reported [16] as microwave assisted synthesis, which reduced total reaction time from several hours to minutes with comparable yields [17].…”