Synthesis, Characterization and Antimicrobial Activities of Novel Heterocycles 8-(3-Chloro-2-(2-hydroxy-3-nitrophenyl)-4-oxoazetidin-1-yl)-4-methylpyrano[2,3-b]phenothiazin-2(11H)-one and 8-(4-(2-(3-Bromo-2-hydroxyphenyl)-3-chloro-4-oxoazetidin-1-yl)phenyl)-4-methylpyrano[2,3-b]phenothiazin-2(11H)-one Derivatives

Phenothiazines [1-3] are of major significance in heterocyclic chemistry. They comprise a tricyclic system which is constituted by two benzene rings and an internal ring containing sulphur and nitrogen [1]. They were primarily employed as dyes in the textile industry during the 19th century, but with new evidence they have been shown to possess excellent antipsychotic properties and are employed in the treatment of schizophrenia and other conditions. Their medicinal importance started becoming evident during the 20th century when methylene blue, a common dye, was found to be an efficient antimalarial and antiseptic drug [1-4]. Phenothiazine's general molecular formula is C₁₂H₉NS and contains N and S atoms in the center. The presence of such configuration renders them highly reactive and amenable for further alterations [5]. The presence of these moieties impacts their electronic nature, lipophilicity, and planar geometry in such a way that it facilitates their binding/attachment to numerous biological target sites [6]. The central nitrogen atom is a significant target site for numerous acetylations, alkylations, or condensations with aldehydes, which inadvertently affects binding affinity to dopamine D₂ receptors, histamine H₁ receptors, and various other CNS-related targets and is pivotal in the development of antipsychotics, antihistamines, and antiemetics [7-10]. Besides this, it has great significance in blood-brain barrier penetration, thereby improving its utilization in medication of CNS-related diseases [11].

β-Lactams comprise a four-membered cyclic amide where the nitrogen atom is attached to the β-carbon relative to the carbonyl group and hence are also known as azetidinones [12-15]. These are quite famous among medicinal chemists. These molecules are among the base scaffolds of many useful antibiotics such as penicillins, cephalosporins, carumonam, aztreonam, thienamycin, and nocardicins [16-19]. The first β-lactam was synthesized in 1907 by Staudinger, but it was only after 1943 that research on these molecules gained momentum as more of the compounds showed intense biological activities such as antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, anticonvulsant, hypotensive, hypnotic, antitubercular, and vital against combating many serious diseases [20-23].

Since the discovery of the coumarin molecule in 1820, it has gained an exclusive place in heterocyclic medicinal chemistry. It is basically 2H-1-benzopyran-2-one [24-27]. It displays a wide spectrum of biological activities such as platelet aggregation inhibition, anticonvulsant, antiviral, anticoagulant, antifungal, anti-HIV, anticarcinogenic, antihistaminic, and antitubercular [28-30]. Coumarin synthesis can be achieved through various chemical reactions such as Pechmann, Perkin, Knoevenagel, and Reformatsky. Among all these, Pechmann condensation is the most frequent method adopted for the synthesis of coumarin [31].