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There is a crucial medical need for the progress of new antibacterial agents with new and more efficient mechanisms. Schiff bases are stated to have a wide range of pharmacological activities, including antimicrobial, antibacterial, antifungal, antioxidant, and anticancer activities, which are largely due to the distinguishing C=N group. Furthermore, heterocyclic compounds containing acyclic hydroxylated side chains, for example, acyclovir (ACV), are an essential class of antiviral acyclonucleosides. Therefore, this work was to synthesize and evaluate a new series of acyclovir analogues bearing a Schiff base moiety. Some of Schiff's bases synthesis in an ethanolic solution of drug, aldehydes, and glacial acetic acid as a catalyst followed in the synthesis of substituted acyclovir drug compounds. In this work, two new series of acyclovir analogues bearing a Schiff base moiety were Synthesised, characterized, and confirmed by various spectral techniques like FTIR, CHN, and 1HNMR spectra, in addition to melting point and retardation factor (Rf.). The biological activity of synthesized Schiff base compounds measured against a panel of various bacteria. The results revealed that these compounds showed antibacterial activity against Gram-positive bacteria such as bacillus and Gram-negative bacteria such as proteus, E-coli, pseudomonas, and klebsiella. It concluded that synthesized Schiff base compounds showed higher antibacterial activity than acyclovir that they derived from it.
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