Abstract
abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.
Highlights
Oxadiazoles comprise four different classes, where 1,3,4-oxadiazoles are more important and are present in a number of biologically active molecules. (Renukadevi, Birada, 1999)
We report the synthesis of some new N-substituted derivatives of 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol2-yl]sulfanyl}acetamides
This paper reports the synthesis of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4oxadiazol-2-yl]sulfanyl}acetamides (8a-w) as potential antibacterial agents, in view of Minimum inhibitory concentration (MIC) values
Summary
Oxadiazoles comprise four different classes, where 1,3,4-oxadiazoles are more important and are present in a number of biologically active molecules. (Renukadevi, Birada, 1999). Due to the propensity of the 1,3,4-oxadiazole ring to undergo a variety of electrophilic and nucleophilic substitution reactions, a large number of derivatives have been synthesized that have remarkable pharmacological, medicinal, and biological activities such as antimicrobial (Rakesh et al, 2010; Zuhair et al, 2008), anti-inflammatory (Dewangan et al, 2010; Omar, Mahfouz, Rahman, 1996), cytotoxic and hypoglycemic (Hasan et al, 2011), anticancer (Bhatnacar et al, 1986), anticonvulsive (Yar, Akhter, 2009), antitubercular (Ali, Shaharyar, 2007), and fungicidal and insecticidal (Zou, Zhang, Jin, 2002; Holla et al, 2004). Inhibitors of the enzyme α-glucosidase are molecules that are used as oral antidiabetic drugs in the treatment of type-2 diabetes mellitus. The inhibitors of this enzyme can delay the release of D-glucose from disaccharides and oligosaccharides from dietary carbohydrates and slow down glucose absorption, resulting in reduced postprandial hyperglycemia (Lebovitz, 1997). A new series of 2-[[5-alkyl/aralkyl-1,3,4-oxadiazol-2-yl]thio]N-[4-(4-morpholinyl)phenyl]acetamides was evaluated by Akhtar et al (2014) for antimicrobial and hemolytic activity; most of them were found to be active against the selected microbial species to a variable extent relative to reference standards, and showed less toxicity as well
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
