Synthesis, Characterization and Antimicrobial Activities of Novel 8-(4-(2-(Substituted/Unsubstituted-Phenyl)-4-oxothiazolidin-3-yl)phenyl)-4-methylpyrano[2,3-b]phenothiazin-2(11H)-one and 4-Methyl-8-(2-methyl-2-(Substituted/Unsubstituted-Phenyl)-4-oxothiazolidin-3-yl)pyrano[2,3-b]phenothiazin-2(11H)-one Heterocycles Derivatives
![Synthesis, Characterization and Antimicrobial Activities of Novel 8-(4-(2-(Substituted/Unsubstituted-Phenyl)-4-oxothiazolidin-3-yl)phenyl)-4-methylpyrano[2,3-b]phenothiazin-2(11H)-one and 4-Methyl-8-(2-methyl-2-(Substituted/Unsubstituted-Phenyl)-4-oxothiazolidin-3-yl)pyrano[2,3-b]phenothiazin-2(11H)-one Heterocycles Derivatives](https://ijoer.com/assets/articles_menuscripts/articlesimages/ijoer-jun-2026-1.webp)
Abstract
The synthesis of oxothiazolidinyl-phenothiazinone derivatives was carried out starting from the condensation of resorcinol and acetoacetic ester, which gives coumarin. Simultaneously, synthesis of cyclic thiazolidin-4-one was done by condensation of aromatic substituted/unsubstituted aldehyde-benzidine and aromatic substituted/unsubstituted aldehyde-benzene-1,4-diamine with thioglycollic acid in the presence of ZnCl₂ in trace amounts. Subsequently, substituted-amine reacted with coumarin in the presence of ZnCl₂ to yield amino-thiazolidin-4-one, and further cyclization took place. The final phenothiazinone heterocycles were synthesized in the presence of sulfur powder and iodine. The structures of the novel synthesized derivatives were established by elemental analysis, UV, FT-IR, ¹H-NMR, and mass spectra. The obtained derivatives exhibited excellent to moderate antibacterial and antifungal activity.
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Introduction
Phenothiazine is amongst the primary molecular synthons involved in the synthesis of antipsychotic drugs. It is a tricyclic compound of immense usage [1-3] in the manufacturing of emetics, antihistamines, anticancer [4-5], antifungal, anti-inflammatory, antitubercular, antioxidant, antileishmanial, and antimalarial treatments. These compounds exhibit extensive antimicrobial activities apart from their usage in psychiatric treatments. These compounds were synthesized in 1883 by Bernthsen. He was evaluating the proof of the structural studies on Lauth's Violet and methylene blue. These compounds [6-9] are attributed with optoelectrochemical and photophysical properties. Substituted phenothiazines have a desirable market in the pharmaceutical industry owing to their widespread capabilities to address a large number of chronic illnesses.
Phenothiazines work by modulating efflux pumps, acting as human cholinesterase inhibitors, characterized as multidrug-resistant reversal in many instances, and causing membrane disruption. Targeted alteration in the phenothiazine core is evaluated for the different biological properties [10-16] of the molecule. A vast body of documents highlights 10H-phenothiazine and its derivatives as playing crucial roles in biological, medicinal, and industrial applications. They are of immense value in CNS activity and thus are major parts of antipsychotic drugs. They possess two active sites at positions 2 and 10 which are hugely responsible for the various kinds of substitutions and chemical rearrangements undergone by the molecules.
Conclusion
The synthesized pyrano[2,3-b]phenothiazin-2(11H)-one derivatives exhibited significant antimicrobial activity. The derivatives 6e (p-NO₂-phenyl) and 7d (p-Br-phenyl) were the most potent antibacterial agents against E. coli with MIC = 6.25 μg/ml, whereas 7c (p-OH-phenyl) and 7d (p-Br-phenyl) exhibited excellent antifungal activity against C. albicans (MIC = 12.5 μg/ml and 6.25 μg/ml respectively). Compound 6f (3-OH,4-OCH₃-phenyl) was the most active derivative against A. niger (MIC = 12.5 μg/ml). These results indicate that incorporation of OH, NO₂, Br, and OCH₃ substituents on the phenyl ring substantially influences antimicrobial potency and provides valuable leads for the development of new antimicrobial agents.
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