Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

Abstract

The notable advancing in the medicinal chemistry arena against infectious diseases has resulted in the discovery of numerous valuable antimicrobial drugs that saved millions of lives throughout the last few decades. Nevertheless, the continuous reporting of multi-drug resistant strains of a number of diverse germs makes the need for novel broad-spectrum anti-infective agents still exists. Methods: Three series of ring-equivalent tricyclic benzo[h]quinazolines (compounds IIIa,b, IVa,b and Va,b), benzo[h]quinolines (compounds VIa-g, VIIa-c and VIIIa-c), and naphthaleno[d]thiazoles analogs (compounds X & XIa-e ) were designed as bioisosteres and synthesized. Benzo[h]quinazolines were respectively obtained via treating chalcones IIa,b with urea, thiourea and guanidine carbonate in basic medium The one-pot reactions of 6-methoxy-1-tetralone I with different aromatic aldehydes and active methylene- containing agents namely ethylcyanoacetate, malononitrile and thiocyanoacetamide in the presence of excess ammonium acetate afforded benzo[h]quinolines compounds VIa-g, VIIa-c and VIIIa-c respectively. Naphthaleno[d]thiazoles X & XIa-e were yielded upon cyclocondensation of the bromotetralone IX with thiourea and aldehydethiosemicarbazones. The chemical structures of the synthesized agents were elucidated based on their spectral data and elemental analyses. Results: The antimicrobial activity of some of the synthesized compounds was screened and only 2-bromo derivative IX and aminothiazole compound X exhibited broad antimicrobial effectiveness. The antifungal MIC value of X was1.85 mg/mL. Conclusion: The new synthesized compounds, designed as bioisosteres, showed excellent potency against the tested gram (+) bacterial and fungal strains compared to reference drugs. Keywords: