1,2,4-Oxadiazole/2-Imidazoline Hybrids: Multi-target-directed Compounds for the Treatment of Infectious Diseases and Cancer

Abstract

Replacement of amide moiety with the 1,2,4-oxadiazole core in the scaffold of recently reported efflux pump inhibitors afforded a novel series of oxadiazole/2-imidazoline hybrids. The latter compounds exhibited promising antibacterial activity on both Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas fluorescens) strains. Furthermore, selected compounds markedly inhibited the growth of certain drug-resistant bacteria. Additionally, the study revealed the antiproliferative activity of several antibacterial frontrunners against pancreas ductal adenocarcinoma (PANC-1) cell line, as well as their type-selective monoamine oxidase (MAO) inhibitory profile.

π–π Noncovalent Interaction Involving 1,2,4- and 1,3,4-Oxadiazole Systems: The Combined Experimental, Theoretical, and Database Study

“…Among all the four oxadiazole types, 1,2,4- and 1,3,4-isomers are the most investigated for medicinal applications [ 23 ], and they are present in numerous marketed drugs, such as the Ataluren [ 25 ], Azilsartan [ 26 ], Opicapone [ 27 ], Naldemedine [ 28 ], and Raltegravir [ 29 ]. Moreover, many oxadiazole derivatives have been studied as antibiotics [ 30 , 31 , 32 , 33 , 34 ], fungicides [ 35 ], antivirals [ 36 ], anticancer [ 37 , 38 , 39 ], and anti-inflammatory [ 40 , 41 , 42 ] agents, neuroprotectors [ 43 , 44 , 45 ], as well as antidiabetic drugs [ 46 ] in recent years. This significantly stimulates further structural and theoretical studies on various noncovalent interactions involving oxadiazole-based compounds.…”

Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity

“…As shown in Table 1, the corresponding acylamidine 2a was obtained only in the presence of polar protic solvents (entries 8-11); however, the desired product was obtained in good yield and in a shorter time by heating the reaction in methanol (entry 12). Interestingly, formic acid could also be used as a reducing agent (entry [10][11]. The use of zinc dust or the absence of catalyst did not produce the desired product (entry 6-7).…”

“…1,2,4-Oxadiazoles are five-membered heterocycles that have been widely studied for their valuable applications ranging from the pharmaceutical field to material science [1]. The use of a 1,2,4-oxadiazole ring as an isosteric replacement of esters and amides increased their presence in medicinal chemistry projects [2] with biological applications ranging from the treatment of nonsense mutations [3,4] and Alzheimer's disease (AD) [5][6][7] to antibiotics [8][9][10] and antitumorals [11,12]. Applications in the field of materials chemistry, such as liquid crystals [13] metal sensors [14], OLED [15], energetic materials [16] and gas sorbing/releasing systems [17][18][19], have been reported.…”

Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

“…Recently, Shetnev A. and collaborators discovered novel 1,2,4-oxadiazole-2-imidazole hybrids as analogs of new class of efflux pump inhibitors presented by Haynes K. M. et al [107,114]. Unfortunately, during the in vivo test, the instability of amide moiety of the aforementioned efflux pump inhibitors has been observed.…”