Synthesis, Antibacterial, and Antifungal Evaluation of New Class of Pyrimido[4,5-d]pyrimidine, Pyrazolo[3,4-d]pyrimidine, and Pyrimido[4,5-b]quinoline Derived from α,α-Ketene Dithioacetals as fused Five and Six-membered Heterocycle Derivatives

Abstract A novel heterocyclic compounds containing pyrimido[4,5-d]pyrimidine (IIIa–IIIb) and (IVa–IVb), pyrazolo[3,4-d]pyrimidine (Va'–Ve') and (VIa'–VIe'), and pyrimido[4,5-b]quinoline (VIIa'–VIIe') and (VIIIa'–VIIIe') were designed and synthesized from the starting materials, 5-(bis(methylthio)methylene)-1,3-diphenylpyrimidine-2,4,6(1H,3H,5H)-trione (IIa) and 5-(bis(methylthio)methylene)-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (IIb) as efficient α,α-ketene dithioacetals is reported. The synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the method for synthesis along with antimicrobial evaluation of these newly synthesized compounds as antibacterial agents against the bacterial strains, like E. coli, B. subtilis, S. aureus, and P. aeruginosa also as antifungal agents against B. cinerea, C. arachidicola, A. solani, G. zeae, S. sclerotiorum, and R. cerealis. Preliminary bioassay showed that most of them exhibited certain-to-excellent antibacterial and antifungal activity. Among all the evaluated compounds, it was found that the synthesized compounds (IVb) and (VIIIc') showed the outstanding antibacterial activity (100%) against the strains E coli and S. aureus respectively comparable to the standard drug Ciprofloxacin at the same concenteration while the others exhibited better antifungal activity at 100 µg/mL. The outstanding antifungal activity (>90%) comparable to the positive controls trifloxystrobin and azoxystrobin exhibited by (VIIIc') against B. cinerea, (IVb) and (Vc') against A. solani, (IVb) against S. sclerotiorum alongwith compounds (VIb'–VIc') against R. cerealis. The structures of all the new synthesized compounds were elucidated by elemental analysis, IR, 1H NMR, and 13C NMR.