Dibasic Derivatives of Phenylcarbamic Acid Against Mycobacterial Strains: Old Drugs and New Tricks?

In order to provide a more detailed view on the structure⁻antimycobacterial activity relationship () of phenylcarbamic acid derivatives containing two centers of protonation, 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium oxalates (⁻)/dichlorides (⁻) as well as 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(di-propylammonio)propyl]azepanium oxalates (⁻)/dichlorides (⁻; alkoxy = butoxy to heptyloxy) were physicochemically characterized by estimation of their surface tension (γ; Traube's stalagmometric method), electronic features (log ; UV/Vis spectrophotometry) and lipophilic properties (log ; isocratic RP-HPLC) as well. The experimental log dataset was studied together with computational logarithms of partition coefficients (log ) generated by various methods based mainly on atomic or combined atomic and fragmental principles. Similarities and differences between the experimental and lipophilicity descriptors were analyzed by unscaled principal component analysis (PCA). The activity of compounds ⁻ was inspected against CNCTC My 331/88 (identical with HR and ATCC 2794, respectively), HR ATCC 25177, CNCTC My 235/80 (identical with ATCC 12478), the 6509/96 clinical isolate, DSM 44162, CNCTC My 330/80 (identical with ATCC 25291), ATCC 700084 and CAMP 5644, respectively. susceptibility of the mycobacteria to reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as well. A very unique aspect of the research was that many compounds from the set ⁻ were highly efficient almost against all tested mycobacteria. The most promising derivatives showed values varied from 1.9 μM to 8 μM, which were lower compared to those of used standards, especially if concerning ability to fight HR ATCC 25177, DSM 44162 or CNCTC My 330/80. Current biological assays and systematic studies based on PCA approach as well as fitting procedures, which were supported by relevant statistical descriptors, proved that the compounds ⁻ represented a very promising molecular framework for development of 'non-traditional' but effective antimycobacterial agents.