Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents

Cinnamic Acid Derivatives and Their Biological Efficacy

“…Compound 10 was 20 times less active when compared to cinnamic acid. Compounds having electron-donating substituents on the para position of the phenyl ring (11)(12)(13) were inactive with IC50 ˃30 µg/mL [24]. Based on the Table 1, compounds 3 and 4 were the best inhibitors of C. lunatus growth.…”

“…However, compound 24 displayed high IC 50 value greater than 30 µg/mL suggesting the nature of the fluorine substituent was also important [24]. For the compounds with halogen substitutes on the phenyl ring, the position, number of substituents and the type of halogen affected the biological activity of the compounds.…”

“…Atmaram Upare et al synthesized cinnamic acid derivatives (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) (Figure 4) in which the carboxyl group was replaced with bioisostere 1,2,4-oxadiazole followed by substituting the phenyl ring of the cinnamic acid resulting in a series of novel styryl oxadiazoles. The compounds were tested in vitro at day 8 for their anti-tubercular activity against H37Ra strain of Mycobacterium tuberculosis (Table 2).…”

“…Compound 17 with a 4-fluoro phenyl ring substitution was the most active of all the compounds containing fluorine with IC50 =0.36 µg/mL indicating that fluoro substitution favored anti-tuberculosis activity of the synthesized compound. However, compound 24 displayed high IC50 value greater than 30 µg/mL suggesting the nature of the fluorine substituent was also important [24]. The introduction of an electron-withdrawing group improved their antibacterial activity (i.e., compounds 20 and 21).…”

Diastereoselective Opening of Bridged Anhydrides by Amidoximes Providing Access to 1,2,4‐Oxadiazole/Norborna(e)ne Hybrids

“…The 1,2,4‐oxadiazole ring is a well‐known pharmacophore found in a number of active pharmaceutical ingredients (APIs) for various therapeutic areas: ataluren (treatment of Duchenne muscular dystrophy), azilsartan (hypertension medication), prenoxdiazine (cough suppressant), and Naldemedine (treatment of opioid‐induced constipation) Additionally to these applications, 1,2,4‐oxadiazoles are actively used to develop a novel therapy against diverse cancer types, metabolic disorders, age‐related diseases, as well as infections, including tuberculosis, methicillin‐resistant Staphylococcus aureus (MRSA), and vancomycin‐resistant Enterococcus (VRE) . Moreover, recently some 1,2,4‐oxadiazole derivatives were recognized as isoform‐selective inhibitors of human carbonic anhydrase (hCA), sphingosine‐1‐phosphate agonists, carbazole‐based cannabinoid receptor subtype 2 (CB2) ligand, and anticonvulsant agents …”