Design, Synthesis and Pharmacological evalution of 1,3,4-Oxadiazole Derivatives As Collapsin Response Mediator Protein 1 (CRMP 1) Inhibitors.

CONTEXT: objective: The series of 2-(4-Phenylamino)-N-(5-((4-nitrophenoxy)methyl) -1,3,4-oxadiazol-2-yl)acetamide (5a-5e) and substituted N-(5-(Phenoxymethyl)-1,3,4-oxadiazol-2-yl)-2-(phenylamino)acetamide (5f-5i) were designed, synthesized and investigated for Collapsin response mediator protein 1 (CRMP 1) inhibitors as small lung cancer.

DESIGN: Design of compounds was done by literature review and molecular docking studies in iGEMDOCK 2.0.

METHODS AND MATERIAL: Novel 1, 3, 4 Oxadiazole derivatives were synthesized and characterized by melting point, TLC, IR Spectroscopy, Mass spectroscopy and 1H NMR. In vitro biological evaluation was performed on NCI-H2066 cell line for different concentrations 10-1000µM by telomeric repeat amplification protocol assay. The assay of telomerase in cellular extracts was modified from the PCR-based telomeric-repeat amplification protocol (TRAP), using the oligonucleotides TS and CX.

RESULTS: Novel substituted 2-(4-Phenylamino)-N-(5-((4-nitrophenoxy)methyl)-1,3,4-oxadiazol-2-yl) acetamide (5a-5e) and substituted N-(5-(Phenoxymethyl)-1,3,4-oxadiazol-2-yl)-2-(phenylamino) acetamide (5f-5i) were synthesized, and characterized using spectral and analytical data. All compounds have shown considerable % inhibition of Cell Growth with respect to Bevacizumab, but compound 5a and 5f were equipotent with respect to activity as compared to standard Bevacizumab.

CONCLUSION: Amongst the hybrids, p-nitro substituted derivative (5a) and p-chloro substituted (5f) showed highest activity against human lung cancer cell line NCI-H2066 by TRAP assay.