Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies

Abstract The process of creating a series of 3-amino-1-aryl-8-methoxy-1 H -benzo f chromene-2-carbonitriles ( 4a-q ) involved reacting 6-methoxynaphthalen-2-ol ( 1 ), the appropriate aromatic aldehydes ( 2a-q ), and malononitrile ( 3 ) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1 H -benzo f chromene-2,8-dicarbonitrile ( 6a, d, e ) was unsuccessful when 6-cyanonaphthalen-2-ol ( 5 ) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA) , Staphylococcus aureus , Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives ( 4 m, i, k ) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br ( 4c, e ) and a double bromine at 3,5-positions with a single methoxy group at 2-position ( 4n ), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated ( 4a, b, d, f ), dihalogenated ( 4 g, h, j, l ) or trisubstituent phenyl ring ( 4o, p, q ). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives ( 4a-f, g-q ) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g , revealing bactericidal effects. Lastly, SAR and molecular docking were studied.