Synthesis and antiproliferative activity of novel (+)- usnic acid analogues

• Published in: Journal of asian natural products research Vol. 22; no. 6; pp. 562 - 577
• Main Authors: Venkata Mallavadhani, Uppuluri, Vanga, Nagi Reddy, Balabhaskara Rao, Kancharana, Jain, Nishanth
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-06-2020; Taylor & Francis Ltd
• Subjects: (+)- usnic acid; Antineoplastic Agents; Antiproliferative activity; Antiproliferatives; Apoptosis; Benzofurans; Biotechnology; Breast; Cancer; Cell cycle; cell cycle arrest; Cell Line, Tumor; Cell Proliferation; Cervix; Drug Screening Assays, Antitumor; enamine; Female; HeLa Cells; Humans; Imines; Molecular Structure; NMR; Nuclear magnetic resonance; Pancreas; pyrazole; Pyrazoles; Structure-Activity Relationship; Synthesis; Tumor cell lines; (+)- usnic acid; pyrazole; apoptosis; Antiproliferative activity; cell cycle arrest; enamine
• ISSN: 1028-6020; 1477-2213
• DOI: 10.1080/10286020.2019.1603220

Twenty one novel (+)- usnic acid-based analogues belonging to three classes such as enamines, imines, and pyrazoles were synthesized. All the synthesized compounds were characterized by their spectral data (
1
H NMR,
13
C NMR, IR, and HRMS). The synthesized compounds were evaluated for their antiproliferative activity against a panel of four human cancer cell lines including HeLa (cervix), MDA-MB-231 (breast), A549 (lung), and MiaPaca (pancreas) by employing SRB cell proliferation assay. Screening results indicated that all synthesized compounds showed enhanced activity than the parent compound. Most significantly, compounds 2e and 4a showed potent antiproliferative activity against all the cancer cell lines tested. Compounds 2e and 4a arrested the cell cycle in G2/M phase and induced apoptosis in HeLa cells. In view of significant antiproliferative activity, compounds 2e and 4a can be considered as lead molecules for further development.