Facile Synthesis, Characterization, and Antimicrobial Evaluation of Novel Heterocycles, Schiff Bases, and <i>N</i>-Nucleosides Bearing Phthalazine Moiety

Abstract

The present work describes convenient synthesis of the novel Schiff bases 5a and b by reacting phthalazinones 4a and b with 4-methoxybenzaldehyde Reaction of the Schiff bases with phenylisothiocyanate afforded diazetidine derivatives 7a and b. Also, compounds 4a and b reacted with 2-bromoglucoside tetraacetate giving peracetylated N-glycosides 6a and b, which were deacetylated to afford N-glycosylated phthalazinones 8a and b. On the other hand, when compound 3 was treated with POCl 3 /PCl 5 and/or ethyl chloroacetate, chlorophthalazine and ethyl acetate derivatives 9 and 10 were obtained, respectively. Hydrazinolysis of compounds 9 and 10 produced the hydrazino and hydrazide derivatives 11 and 12, respectively. When compound 11 reacted with 2-furanaldehyde, acetic anhydride, and/or carbon disulphide, it gave compounds 13-15, respectively. Treatment of the hydrazide 12 with aromatic aldehydes, acetic anhydride, ethyl acetoacetate, acetyl acetone, ammonium thiocyanate, and/or phthalic anhydride furnished compounds 17-21. Meanwhile, reacting Schiff base 22 with the chlorophthalazine derivative 9 produced compound 23, which on treatment with furoyl chloride produced compound 24. The structures of the novel compounds were confirmed by IR, 1 H-NMR, 13 C-NMR, MS, and elemental analysis. The newly synthesized compounds were tested against Bacillus subtilis and Staphylococcus aureus as Gram-positive bacteria, Escherichia coli and Pseudomonas aurignosa as Gram-negative bacteria, and Candida albicans and Aspergillus niger as fungi strains. Compounds 5a and b, 23, and 24 showed greater antimicrobial activity than the stranded compounds, suggesting that they could be considered as promising antimicrobial agents.Key words phthalazin-1-one; N-glycosylated phthalazinone; Schiff base; diazetedine; antimicrobial activity Phthalazines as N-heterocycles have received considerable attention in the literature as a consequence of their role as pharmacophore.1,2) Recently, they are derived from a wide range of biologically active natural products, troponoid family.3) A novel series of N-substituted-4-phenyl/benzylphthalazin-1-ones, phthalzine-1,4-dione showed antitumor activity. were prepared from the corresponding phthalazinones. Moreover, many substituted and fused phthalazine and phthalzinone derivatives exhibited antimicrobial activity. 23-26)On the basis of the above findings and in continuation of our research interest in the synthesis of novel biologically active heterocycles, [27][28][29][30][31] and with the aim of preparing new derivatives of phthalazine with potential pharmacological activity, we report here the synthesis of novel Schiff bases containing phthalazine moiety, phthalazinone and fused phthalazine derivatives, followed by evaluation of their antimicrobial activity against different strains of bacteria and fungi, where most of synthesized compounds exhibited a moderate to a strong antimicrobial activities. Some of the tested compounds showed antimicrobial activity higher than the reference compounds. Results and D...

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

“…It also acts as a center structure for different bioactive molecules because of its easy fictionalization at different substitution patterns and their roles as pharmacophore . Some of O ‐alkyl‐phthalazine derivatives were monitored in vitro for their antimicrobial effect, and the energy variance between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) plays a significant role in the electronic studies of these molecules by quantum chemical calculations that reflects the relation between delocalization, electron distribution, and chemical reactivity with kinetic stability of the compound . Phthalazine derivatives were announced to acquire anticonvulsant , antitumor , antihypertensive, antithrombotic , antidiabetic , antitrypanosomal , anti‐inflammatory , cardiotonic , and vasorelaxant activities.…”

Synthesis of Novel Substituted Tetrahydropyrimidine Derivatives and Evaluation of Their Pharmacological and Antimicrobial Activities

“…Heterocyclic compounds have been widely utilized in synthesis of pharmacologically active‐compounds . In particular, pyrimidines and fused pyrimidines as key building units of DNA and RNA revealed the fact that their derivatives exhibit diverse pharmacological activities such as anticancer , antiviral , anti‐inflammatory , antioxidant , antibacterial,‐and antifungal‐agents .…”

Antimicrobial and Cytotoxic Activities of Some Novel Heterocycles Bearing Pyrazole Moiety

“…For the aforementioned biological activity and in continuation of our efforts in the synthesis of biologically active heterocycles , we prepared an enaminonitrile‐containing pyrazole moiety, which was subjected to electrophilic and nucleophilic reactions in order to prepare novel heterocyclic compounds and study their antimicrobial and anticancer activities. The newly synthesized compounds were evaluated against Gram‐positive Staphylococcus aureus and Bacillus subtilis and Gram‐negative Escherichia coli and Pseudomonas aeruginosa .…”