Design and Synthesis of Arylthiophene-2-Carbaldehydes via Suzuki-Miyaura Reactions and Their Biological Evaluation

Abstract

A series of various novel 4-arylthiophene-2-carbaldehyde compounds were synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling with different arylboronic pinacol esters/acids. The synthesized products were screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO) scavenging capabilities and interestingly, almost all products turned out to have good activities. 3-(5-Formylthiophene-3-yl)-5-(trifloromethyl)benzonitrile (2d) revealed excellent antibacterial activity, showing an IC 50 value of 29.7 µg/mL against Pseudomonas aeruginosa, compared to the standard drug streptomycin with an IC 50 value 35.2 µg/mL and was also found to be the best NO scavenger, with an IC 50 value of 45.6 µg/mL. Moreover, 4-(3-chloro-4-fluorophenyl)thiophene-2-carbaldehyde (2i) exhibited a superior haemolytic action and an outstanding urease inhibition, showing an IC 50 value of 27.1 µg/mL.

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

“…Ali and coworkers assessed the antiurease activity of diverse 5-aryl-thiophene-2-carbaldehydes [68] . The authors observed a trend in which electron-withdrawing groups were more active at inhibiting the enzyme than their electron-donating counterparts, highlighting the di-halogenated compound ( 44 – Series A; Scheme 16 ) as the most active of the series [68] .…”

One Pot Selective Arylation of 2-Bromo-5-Chloro Thiophene; Molecular Structure Investigation via Density Functional Theory (DFT), X-ray Analysis, and Their Biological Activities

“…Thiophene moiety is found to be very potent in various biological activities [ 15 , 16 , 17 ]. Anti-urease and nitric oxide (NO) scavenging activity of a series of 2-amino-6-arylbenzothiazoles were examined by Gul et al [ 11 ].…”

“…Anti-urease and nitric oxide (NO) scavenging activity of a series of 2-amino-6-arylbenzothiazoles were examined by Gul et al [ 11 ]. Various 4-arylthiophene-2-carbaldehydes showed moderate to excellent ability against antibacterial, anti-urease, hemolytic, and antioxidant activities [ 16 ]. We became interested in synthesizing unsymmetrical bis-aryl (Ar and Ar′) substituted thiophene by taking the advantage of difference of reactivity of chloro and bromo moiety on thiophene ring.…”

Regioselective synthesis of 2-(bromomethyl)-5-aryl-thiophene derivatives viapalladium (0) catalyzed suzuki cross-coupling reactions: as antithrombotic and haemolytically active molecules

“…The Suzuki–Miyaura cross-coupling reaction, which produces biaryls has proven to be the most important building blocks in organic synthesis owing to their industrial applications. We have previously reported the synthesis of arylthiophenes by regioselective Suzuki cross-coupling reactions and they were potentially studied as pharmaceutical agents [ 26 , 27 ].…”