Synthesis, Single‐Crystal X‐Ray, Hirshfeld and Antimicrobial Evaluation of some New Imidazopyridine Nucleus Incorporated with Oxadiazole Scaffold

Abstract

To avert the menace of pathogens in medical parlance, emerging attractive strategy is combining two different active fragments in a single molecule for scientific solutions. Trisubstituted imidazo[1,2-a]pyridine-carboxylate was engrossed as a hybrid with oxadiazole. The three dimensional and crystal structures of compounds 3-[5-(2-chlorophenyl)-1,3,4-oxadiazol-(4 e) were determined using single crystal X-ray diffraction studies and their crystal packing was analyzed using Hirshfeld surface computational analysis. The molecular conformation of 4 c (planar) and 4 e (twisted) and crystal packing is different and this may be due to substitution effect. In addition, both compounds have common intermolecular interactions of the type C-H…π and intercontacts H…H contributes more to the Hishfeld surfaces. Screening for microbial activity acknowledged, 2,8-dimethyl-3-[5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl] imidazo[1,2-a]pyridine (4 f) and 6-chloro-2-methyl-3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]imidazo[1,2-a]pyridine (4 g) as most effective against Staphyllococus aureus, over all other derivatives. Meanwhile, 4 f also showed pronounced antifungal activity against Candida albicans. Further 4 f was endorsed by time kill assay as bactericidal in its action.[a] S.

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

“…Kuthyala et al [ 15 ] have studied the in vitro antimicrobial activity of some oxadiazolo-imidazopyridine hybrid derivatives. The synthesis was straight, involving a cyclocondensation reaction of hydrazonyl-imidazopyridine 27 with different benzoic acids, when the corresponding oxadiazolo-imidazopyridine hybrids 28a – j were obtained, Scheme 7 .…”

Imidazo[1,2‐a]pyridine as a promising scaffold for the development of antibacterial agents

“…The hybrid compound 15f exhibited excellent antibacterial activity against [ S. aureus ] with MIC values of 3.12 ± 0.9 μg/ml but it showed moderate activity against [ B. subtilis ] and very poor activity against Gram ‐ve bacteria with MIC 50 and 150 μg/ml respectively. The Methyl and nitro substitution on imidazo[1,2‐a]‐pyridines highly increased the antibacterial properties whereas halogen substitution (5‐Cl) on imidazopyridine ring showed slight decrease in activity against [ S. aureus ] (Scheme 3) [64].…”

“…3‐substituted imidazo[1,2‐a]pyridine molecules also exhibit a wide range of biological applications along with the maximum antibacterial activity against [ M. tuberculosis] (ATCC‐27294) and several Gram +ve and Gram ‐ve microorganisms like [ E. coli ] (ATCC‐25922), [ S. aureus ] (ATCC‐ 9144), [ K. pneumoniae ] (ATCC‐13883), and [ B. subtilis ] (ATCC‐6051) [64, 65, 68–70, 75, 76].…”

Towards the Synthesis of Imidazopyridine Derivatives: Characterization, Single Crystal XRD, Hirshfeld Analysis, and Biological Evaluation

“…Defined as drug prejudice, imidazo[1,2‐a]pyridine is a privileged scaffold in medicinal chemistry and a source for new drug‐like compounds [6] . Imidazopyridine represents a promising area with its ability to target as an analgesic, anti‐cancer, antipyretic, antiprotozoal, anti‐inflammatory agents, etc [7] . It has also been reported as an inhibitor for several enzymes like kinase‐3β (GSK‐3)6, glycogen synthase, protein kinase, [8] thus proving to be a key component in inhibiting cell proliferation.…”

“…[6] Imidazopyridine represents a promising area with its ability to target as an analgesic, anti-cancer, antipyretic, antiprotozoal, anti-inflammatory agents, etc. [7] It has also been reported as an inhibitor for several enzymes like kinase-3β (GSK-3)6, glycogen synthase, protein kinase, [8] thus proving to be a key component in inhibiting cell proliferation. Over the years, triazoles have attracted considerable attention in the field of drug discovery.…”