Synthesis of new triterpenic monomers and dimers as potential antiproliferative agents and their molecular docking studies

• Published in: European journal of medicinal chemistry 2018-01, Vol.143, p.948-957
• Main Authors: Saeed, Aasim, Hussain, Hidayat, Shamraiz, Umair, Rehman, Najeeb Ur, Khan, Husain Yar, Badshah, Amin, Heller, Lucie, Csuk, René, Ali, Majid, Khan, Ajmal, Al-Harrasi, Ahmed
• Format: Article
• Language: English
• Subjects: Antiproliferation; Docking study; Myrrhanone B; Triterpene acid
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2017.10.079

In the current investigation, new monomers of myrrhanone B and lupeolic acid were prepared via reaction of triterpenic acids with linkers in the presence of K2CO3. In addition, new bis-myrrhanone B homodimers, myrrhanone B-myrrhanol B heterodimers, and bis-myrrhanone β-boswellic acids heterodimer were prepared. Evaluation of these compounds on the proliferation of four different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma) and A375 (malignant melanoma) has been performed. It is worth mentioning that compounds 4, 7, 8, 10, and 11 possess potent antiproliferative effect towards HT29 cancer cells with IC50 values of 8.1 μM, 5.4 μM, 8.8 μM, 6.8 μM, and 8.2 μM, respectively. In addition, these compounds display good to moderate antiproliferative activities towards A2780 and A375 with IC50 values ranging from 10.4 to 24.2 μM. Moreover, the molecular docking studies of most active compounds (4, 7, 8, 10 and 11) with six anti-cancer drug targets DHFR, VEGFR2, HER-2/neu, CDK6, hCA-IX and LOX also carried, in order to know the mode of binding interaction and energy of this class of compounds. [Display omitted] •A new series of potent anticancer triterpene acids monomers and dimers were synthesized.•The synthesized compounds were evaluated against four different human cancer cell lines.•Compounds 4, 7, 8, 10, and 11 were potent towards colon cancer with IC50 below 10 μM.•Molecular docking studies of were performed for most active compounds 4, 7, 8, 10 and 11.