Synthesis, Characterization, Antibacterial and Cytotoxic Evaluation of New 6-(Chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile Derivatives and Their Corresponding Furo[2,3-b]pyridine Derivatives

Abstract

The synthesis of a new series of 6-(chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile compounds 2 and 5 and their furo[2,3-b]pyridines bearing heteroaryl substituents 3 and 6 in high yield is reported. The 6-(chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile derivatives (2a-f) and (5a-d) were prepared from the corresponding 3-cyano-(2H)-pyridones (1a-f) and (4a-d) followed by the Thorpe-Ziegler ring cyclization in the presence of sodium methoxide to give the target furo[2,3-b]pyridine derivatives (3a-f) and (6a-d). Proposed structures of the new compounds are based on NMR and mass spectral data. Antibacterial evaluation of (2a-d), (2f), (5a-d), (3a-d), (3f), and (6a-d) derivatives against eight different microorganisms shows no activity towards any of the tested bacteria while compounds (6a ( and (6c ( showed weak antibacterial activity with inhibition zone of 10 mm. Cytotoxic assessment against MCF7 breast cancer cells reveals that 10 of the derivatives were found to decrease cell viability in a dose dependent manner at concentration of 100 μM, but six of them decreased it to less than 50% and had IC50's ranging from 23.3 to 41.2 μM.

Synthesis, characterization, antibacterial activity and cytotoxicity of (1′R,2′S,7a′S)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′‐(aryl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one derivatives

“…Additional studies of the synthesis of a diverse substituted spirooxindoles via 1,3‐dipolar cycloaddition reaction are reported [12–17]. In continuation to our work [18–24], we herein report the synthesis and characterization of (1′R,2′S,7a′S)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′‐(aryl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one, I , derivatives by the reaction of the corresponding 2,5‐dichlorothiophene containing chalcone (2,5‐dichlorothiophene has not been explored extensively), l ‐proline and 2,3‐indolinedione. The molecular, crystal structure and crystal supramolecularity of three derivatives, namely, (1′R,2′S,7a′S)‐1′‐(4‐(tert‐butyl)phenyl)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one, (1′R,2′S,7a′S)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′‐(4‐fluorophenyl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one and (1′R,2′S,7a′S)‐1′‐(3‐Chlorophenyl)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one are also reported.…”

“…The antibacterial activity against the gram‐positive Streptococcus pneumonia and Enterococcus faecalis and the gram‐negative bacteria Escherichia coli , Klebsiella pneumonia , Staphylococcus aureus , Shigella sonei and Salmonella paratyphi according to agar diffusion method described before [24]. Ampicillin was used as a positive standard.…”