Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

Abstract

Several 15,16-epoxy-8,13,14-labdatriene derivatives modified at the C-16 position with a 1,2,4-oxadiazole ring with various substituent in the 5-th position, were obtained via multistep synthesis from 16-formyl derivatives of natural diterpenoid lambertianic acid. The cytotoxicity of furanolabdanoid-based 1,2,4oxadiazoles was evaluated against human cancer cells (CEM-13, MT-4, U-937, MCF-7, MDA-MB-231, MEL-8) using the conventional MTT assays. All the tested diterpenoid-oxadiazole hybrids displayed better cytotoxic activity then lambertianic acid. The activity and selectivity to the cell line increased even further in the compounds containing a chloromethyl substituent in the 5th position of the 1,2,4-oxadiazole ring. Two of the synthesized compounds exhibited high cytotoxic activity against lymphoblastoid cell line CEM-13 (GI 50 0.08-0.34 mM), which was higher that than of the comparative drug Doxorubicin. The antitumor mechanism may be related to apoptosis induction in U-937, MCF-7, and CEM-13 cells.[a] Dr.

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

“…From this screening, compound 55 ( Figure 10) emerged for its remarkable toxicity, with GI50 values of 0.08 ± 0.03 µM on CEM-13, and 0.35 ± 0.11 µM on MT-4. Moreover, cytofluorimetric analysis demonstrated that treatment of U937 cells with 55 induced apoptosis in 46.8% of cells after 24 hours and 84.4% after 48 hours [91].…”

“…Modification of oxadiazole scaffolds through conjugation to bioactive natural products, also represent a promising approach. Mironov et al exploited Furano-diterpenoids of the labdane series, an anti-inflammatory and anti-allergic drug-like [90], to build novel and potent derivatives [91]. In detail, 1,2,4-oxadiazoles were conjugated to labda-8(9),13,15-triene or labda-8(17),13,15-triene core and their antiproliferative activity and GI50 on CEM-13, MT-4 and U937 cells were measured [91].…”

“…Mironov et al exploited Furano-diterpenoids of the labdane series, an anti-inflammatory and anti-allergic drug-like [90], to build novel and potent derivatives [91]. In detail, 1,2,4-oxadiazoles were conjugated to labda-8(9),13,15-triene or labda-8(17),13,15-triene core and their antiproliferative activity and GI50 on CEM-13, MT-4 and U937 cells were measured [91]. From this screening, compound 55 ( Figure 10) emerged for its remarkable toxicity, with GI50 values of 0.08 ± 0.03 µM on CEM-13, and 0.35 ± 0.11 µM on MT-4.…”

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

“…Modification of oxadiazole scaffolds through conjugation to bioactive natural products also represents a promising approach. Mironov et al exploited Furano-diterpenoids of the labdane series, an anti-inflammatory and anti-allergic drug-like [ 90 ], to build novel and potent derivatives [ 91 ]. In detail, 1,2,4-oxadiazoles were conjugated to labda-8(9),13,15-triene or labda-8(17),13,15-triene core and their antiproliferative activity and GI 50 on CEM-13, MT-4 and U937 cells were measured [ 91 ].…”

“…Mironov et al exploited Furano-diterpenoids of the labdane series, an anti-inflammatory and anti-allergic drug-like [ 90 ], to build novel and potent derivatives [ 91 ]. In detail, 1,2,4-oxadiazoles were conjugated to labda-8(9),13,15-triene or labda-8(17),13,15-triene core and their antiproliferative activity and GI 50 on CEM-13, MT-4 and U937 cells were measured [ 91 ]. From this screening, compound 55 ( Figure 10 ) emerged for its remarkable toxicity, with GI 50 values of 0.08 ± 0.03 µM on CEM-13, and 0.35 ± 0.11 µM on MT-4.…”