New hydrazide–hydrazones of isonicotinic acid: synthesis, lipophilicity and in vitro antimicrobial screening

Abstract

This study describes the synthesis, lipophilicity and in vitro antimicrobial assays of 15 new hydrazide-hydrazones of isonicotinic acid. New derivatives were obtained on the basis of the condensation reaction of isonicotinic acid hydrazide with different aromatic aldehydes. The chemical structure of synthesized compounds was confirmed by spectral methods. Experimental lipophilicity of new isonicotinic acid derivatives was determined using reversed-phase thin-layer chromatography. All synthesized compounds were subjected to in vitro antimicrobial assays against reference strains of Gram-positive bacteria, Gram-negative bacteria and fungi belonging to Candida spp. Some of the synthesized hydrazide-hydrazones proved to be significant antibacterial compounds and more potent than commonly used chemotherapeutic agents.

Synthesis andin VitroAntimicrobial Activity Screening of New 3‐Acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline Derivatives

“…Hydrazide-hydrazones of isonicotinic acid (1 -13) have been synthesized and fully characterized by our group previously. [47] Synthesis of 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) 0.001 Mole of appropriate hydrazide-hydrazone of isonicotinic acid (1 -13) was dissolved in 2 mL of neat acetic anhydride and heated under reflux for 3 h. Subsequently, the volatiles were removed under reduced pressure and a saturated aqueous solution of sodium bicarbonate was added to the residue and the mixture was left at room temperature. After 24 h, formed precipitate was filtered off and re-crystallized from ethanol.…”

“…Hydrazide-hydrazones were obtained on the basis of the method described earlier by our group. [47] The 1,3,4-oxadiazolines (14-26) were obtained in good yields (45-79 %). They are stable solids, soluble in DMSO at room temperature.…”

“…The in vitro screening of compounds 14-26 was performed with the use of the broth microdilution method as described earlier by our group [47] and according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute guidelines. [54,55] In microbiology assays, we used a panel of reference and clinical or saprophytic strains of microorganisms from American Type Culture Collection (ATCC).…”

“…[45] Iproniazide, an isoniazid derivative, originally used as an antituberculosis medicine, showed mood elevation in depressed patients, which makes it the first MAO (monoamine oxidase) inhibitor. [46] Due to the broad spectrum of biological activity, especially antimicrobial activity of isonicotinic acid [44,45] and 1,3,4-oxadiazole derivatives, [10 -15] as well as that of hydrazide-hydrazones, reported by our group earlier, [47][48][49][50][51][52] we decided to combine these two pharmacophores in one chemical structure with the hope of obtaining interesting antimicrobial agents.…”

Synthesis of promising antimicrobial agents: hydrazide‐hydrazones of 5‐nitrofuran‐2‐carboxylic acid

“…In our previous research, a series of hydrazide‐hydrazones showed very promising antimicrobial and antifungal activities (Popiołek & Biernasiuk, , , , ; Popiołek, Biernasiuk, et al, ). For instance, a series of nitrofurazone analogues containing hydrazide‐hydrazone moiety synthesized by our group displayed, depending on the compounds and bacterial or fungal strains, higher antimicrobial activity than ciprofloxacin, nitrofurantoin or cefuroxime, which were used as reference substances (Popiołek & Biernasiuk, ).…”