Synthesis and anticancer evaluation of complex unsaturated isosteviol-derived triazole conjugates

Abstract

Background: For the last two decades, diterpenoid isosteviol and its derivatives have gained significant attention for novel chemical transformation in the drug discovery field. Results: An efficient way towards the synthesis of structurally diverse isosteviol derivatives was described here employing unsaturated functionalities as attractive templates for further transformation such as epoxidation. These structurally diverse compounds exhibited promising cytotoxic activities on different types of cancer cell lines, leading to drug discovery derived from natural products for the treatment of cancer. Conclusion: In this work, novel isosteviol derivatives with Michael acceptors were synthesized to expand the diversity and complexity of a class of isosteviol-derived triazole conjugates to facilitate the development of potential antitumor agents.

Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis

“…Previous studies have revealed the biological effects of isosteviol derivatives, including anti-hypertension, anti-inflammation, anti-diarrhea, anti-cancer, anti-viral, and anti-bacterial activity 12 – 16 , 26 . Specifically, isosteviol derivatives were found to inhibit the NF-κB signaling pathway 14 , 26 , 27 , which is closely associated with osteoclast differentiation 18 , 28 , 29 .…”

“…Isosteviol (ent-16-oxobeyeran-19-oic acid), an ent-beyerane tetracyclic diterpenoid, is a stevioside compound that is obtained via acid hydrolysis. Isosteviol derivatives exert a variety of biological effects, including anti-hypertension, anti-inflammation, anti-diarrhea, anti-cancer, anti-viral, and anti-bacterial activity 12 – 16 . NC-8, an isosteviol derivative, has been demonstrated to effectively inhibit the secretion of hepatitis B virus (HBV) surface antigens and HBV core antigens and inhibit the host TLR2/NF-κB signaling pathway 14 .…”

A Review on Azole Derivatives as Potent Anticancer Agents

“…Foremost percentage of all anticancer drugs permitted internationally are either a natural product or their analogues mostly established on the basis of the acquaintance of the pre-existing knowledge of drugs 15 . Recent researches have highlighted the active role of various azole derivatives in the field of anticancer research [16][17][18][19][20][21][22] . It has been evidenced that heterocycles possess azole pharmacophore found privileged structure in medicinal chemistry as well as pharmaceutical industry [23][24][25][26][27] .Aromatic heterocycles are present in numerous molecules of chemical or biological interest, as well as in organic materials for different applications 28 .…”

“…It has been evidenced that heterocycles possess azole pharmacophore found privileged structure in medicinal chemistry as well as pharmaceutical industry [23][24][25][26][27] .Aromatic heterocycles are present in numerous molecules of chemical or biological interest, as well as in organic materials for different applications 28 . On the basis of the existing synthetic approaches and anticancer properties of such heterocycles, this field of research has opened doors for biologists and chemists to design some novel entities with better efficacy through chemical transformations and development of new moieties having broad spectrum therapeutic implications [29][30][31][32][33][34] . In this review, we highlight some areas of current interest in context to azoles and their derivatives as potent chemotherapeutic agents.…”

Synthesis, cytotoxic activity, and 2D‐ and 3D‐QSAR studies of 19‐carboxyl‐modified novel isosteviol derivatives as potential anticancer agents

“…To go deep into the research on isosteviol, a large number of isosteviol derivatives have been obtained by microbial transformation and chemical modification. The typical properties of isosteviol derivatives, such as cytotoxic activities, catalytic performance, as well as supramolecular self‐assembly properties, were further investigated in recent years. Notably, some of the synthetic isosteviol derivatives exhibited remarkable inhibitory activity against cancer cells that captured scientific attention with possible applications in anticancer drugs design and development.…”