Antimicrobial Activity of Quinoline-Based Hydroxyimidazolium Hybrids

Abstract

Eight quinoline-based hydroxyimidazolium hybrids 7a–h were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds 7c–d showed remarkable antifungal activity against Cryptococcus neoformans with a minimum inhibitory concentration (MIC) value of 15.6 µg/mL. Against other opportunistic fungi such as Candida spp. and Aspergillus spp., these hybrids showed MIC values of 62.5 µg/mL. Regarding their antibacterial activity, all the synthetic hybrids demonstrated little inhibition of Gram-negative bacteria (MIC ≥50 µg/mL), however, hybrid 7b displayed >50% inhibition against Klebsiella pneumoniae at 20 µg/mL and full inhibition at 50 µg/mL. Moreover, this hybrid was shown to be a potent anti-staphylococcal molecule, with a MIC value of 2 µg/mL (5 µM). In addition, hybrid 7h also demonstrated inhibition of Staphylococcus aureus at 20 µg/mL (47 µM). Hybrids 7a and 7b were the most potent against Mycobacterium tuberculosis H37Rv with MIC values of 20 and 10 µg/mL (46 and 24 µM), respectively. The 7b hybrid demonstrated high selectivity in killing S. aureus and M. tuberculosis H37Rv in comparison with mammalian cells (SI >20), and thus it can be considered a hit molecule for mechanism of action studies and the exploration of related chemical space.

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

“…In 2019, Insuasty, Abonia, and coworkers synthesised quinoline-based hydroxyimidazolium hybrids 398a-h and evaluated in vitro their antimicrobial activity against two Gram-negative microorganisms, E. coli and K. pneumoniae, Gram-positive S. aureus, and two acid fast slow-growing mycobacteria, Mycobacterium tuberculosis H 37 R v and M. bovis BCG [221]. As shown in Scheme 81, the synthesis of hybrids 398 involved the conversion of 2-chloroquinoline-3-carbaldehydes 399 to 2-oxo-1,2-dihydroquinoline-3-carbaldehydes 400, followed by alkylation of the latter derivatives with n-BuBr or BnBr in DMF in the presence of K 2 CO 3 .…”

“…As shown in Scheme 81, the synthesis of hybrids 398 involved the conversion of 2-chloroquinoline-3-carbaldehydes 399 to 2-oxo-1,2-dihydroquinoline-3-carbaldehydes 400, followed by alkylation of the latter derivatives with n-BuBr or BnBr in DMF in the presence of K 2 CO 3 . Aldehydes 401 were then subjected to reaction with 3-butyl-1-methylimidazolium chloride (402), in MeCN at 80 • C in the presence of AcONa under ultrasonic irradiation to afford the required hybrids 398 in 60-91% yield [221,222]. Compounds 400 were in turn prepared by a Meth-Cohn reaction [223].…”

“…In particular, the reaction involved treatment of a degassed DMF solution of 219 with tris[2-phenylpyridinate-C 2 ,N]iridium(III)[Ir(ppy)3] (3 mol%) followed by irradiation with light generated from an 11 W CFL bulb at 23 °C. The resulting crude compound 220 was treated with propane-1,3-dithiol(221) and TiCl4 in CH2Cl2 at -78 °C affording dithiane 222 in 43% yield. A subsequent nine-step reaction sequence provided bis-azide 223, which was oxidised using Dess-Martin periodinane.…”

“…Molecules 2020,25, x FOR PEER REVIEW 83 of 106 characteristics of both Gram-positive and Gram-negative bacteria. On the other hand, hybrid 398b at concentrations ranging from 30 to 500 µM demonstrated 100% inhibition of S. aureus and at 300 µM demonstrated 100% inhibition of K. pneumoniae, and hybrids 398d, 398e, and 398h displayed moderate growth inhibition against the virulent H37Rv strain with MIC values of 110 µM[221].…”

Visible light induced nano copper catalyzed one pot synthesis of novel quinoline bejeweled thiobarbiturates as potential hypoglycemic agents

“…Quinolines have become important compounds because of their variety of applications in medicinal, synthetic organic chemistry as well as in the field of industrial chemistry [5][6][7][8][9]. Quinoline nucleus is endowed with a variety of therapeutic activities and new quinolone derivatives are known to be biologically active compounds possessing several pharmacological activities being used as antimalarial [10][11][12], antiviral [13,14], anti-inflammatory [15,16], antiprotozoal [17][18][19], antibacterial [20][21][22], antineoplastic [23,24], antioxidant [25,26], antifungal [27,28], analgesic [29,30], cardiovascular [31], and hypoglycemic agent [32,33]. Considering the noteworthy applications in the fields of bioorganic, medicinal, industrial, and synthetic organic chemistry there has been remarkable interest in developing established protocols for their construction and effective methods for the synthesis of quinolines [34][35][36][37][38].…”