Catalyst free sequential one-pot reaction for the synthesis of 3-indole propanoates/propanoic acid/propanamides as antituberculosis agents

A highly efficient catalyst free one pot four component synthesis of highly functionalized three-substituted indole derivatives has been reported. Thus, sequential catalyst free condensation of readily available aldehydes with Meldrum's acid followed by Michael addition of indole resulting three carbon component condensed product and concurrent decarboxylation by the nucleophilic attack of ethanol/water/amines affords three-indole propanoates/propanoic acid/propanamides in affordable yields. Further, synthesized compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain by Alamar blue assay method. Majority of the compounds exhibited the superior activity and specifically compound 4d has MIC 1.6 mu g/ml, which is better than the reference drugs used

Effect of compound 4f on (A) Collagen induced protein phosphorylation (B) A23187 induced γ-glutamyltransferase activity (C) MTT cell viability assay (D) LDH release in platelets.

<p>(A) Lane I- resting platelets (untreated). Lane II- platelets treated with Collagen (1 µg/mL). Lanes III, IV and V- pre-loaded platelets with collagen and incubated with 4f in increasing concentration of 25, 50 and 100 µM respectively. Values are presented as mean ± SEM (n = 5). ***<i>p</i><0.001; significant compared to control. ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001; significant compared to agonist.</p

Effect of compound 4f on A23187 induced (A) Endogenous generation of ROS (B) Intracellular calcium levels (C) Mitochondrial membrane depolarization and (D) Peroxidation of cardiolipin in PRP and washed platelets.

<p>Values are presented as mean ± SEM (n = 5), expressed as percentage increase in DCF fluorescence (for ROS), percentage increase in Fura-2/AM fluorescence (intracellular calcium), Rhodamine 123 fluorescence (ΔΨ<i>m</i>) and NAO fluorescence (cardiolipin), relative to control. ***<i>p</i><0.001; significant compared to control. ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001; significant compared to A23187.</p

Efficacy of Ibuprofen and its derivatives measured in terms of (A) Reduction potential (B) DPPH radical scavenging activity in comparison with Quercetin.

<p>Values are presented as mean ± SEM (n = 5).</p

Effect of compound 4f on A23187 induced (A) Translocation of cytosolic cytochrome C and activation of caspase-3 (B) Caspase-9 and (C) Caspase-3 activities and (D) PS externalization in PRP and washed platelets.

<p>Values are presented as mean ± SEM (n = 5), expressed as percentage increase in (B & C) caspase activity and (D) Annexin V-FITC fluorescence and expressed as percentage increase in apoptotic platelets expressing PS relative to control. ***<i>p</i><0.001; significant compared to control. ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001; significant compared to A23187.</p

Physical and chemical characteristics of new Ibuprofen derivatives.

<p>Physical and chemical characteristics of new Ibuprofen derivatives.</p

Reaction sequence for the synthesis of new Ibuprofen derivatives.

<p>Reaction sequence for the synthesis of new Ibuprofen derivatives.</p