Design, Synthesis and Evaluations of New 10‐Triazolyl‐1‐methoxygenipin Analogues for Their Cytotoxicity to Cancer Cells

Abstract

Genipin 1, derived from geniposide present in the fruit of Gardenia jasminoides Ellis has been reported to show diverse pharmacological activity. In this work, a new series of genipintriazole analogues was designed and synthesized yielding high yields from naturally genipin and their cytotoxicity evaluated against six cancer cell lines. Twenty-seven analogues were obtained using a convenient four-step reaction methods. Six analogues showed higher cytotoxic activity than the original genipin and benzylether-triazolegenipin 5 j exhibited the strongest activity against P-388 and A-549 cancer cell lines with IC 50 values of 2.54 and 4.53 μM. The structure-activity relationships (SARs) study indicated that the introduction of dibenzyl ether, substituted silyl and long chain aliphatic-triazoles at C-10 position of genipin were most effective in improving cytotoxicity. Molecular docking results provided the information for further modification of genipin scaffold for development as cytotoxic agent.

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

“…A significant part of 1,2,3-triazole-containing methoxygenipin derivatives 77 (IC 50 : 4.53-47.18 μm, SRB assay) are active against A549 cells, whereas the parent genipin (IC 50 : > 20.0 μm) is devoid of activity (Silalai et al, 2020). An SAR study implies that the introduction of dibenzyl ether substituted silyl and long-chain aliphatic groups into the C-10 position of the genipin moiety could increase the activity.…”

1,2,3‐Triazole hybrids as anticancer agents: A review

“…[50] 1,2,3-Triazole containing methoxygenipin derivatives 33 and 34 were active against A549 cells, with IC 50 values of 4.81 and 4.53 μM, respectively, whereas the parent genipin (IC 50 > 20.0 μm) was devoid of activity. [51] 2.2 | 1,2,3-Triazole-linked carbohydrate/ nitrogenous base hybrids 1,2,3-Triazole derivatives linked to carbohydrate units 35 showed moderate cytotoxicity, with IC 50 values of 88.8 and 97.5 μM against human liver cancer (HepG-2) and human breast adenocarcinoma (MCF-7) cell lines. The moderate anticancer activity of compound 35 could be attributed to its low binding affinity to the examined biological targets.…”

Synthesis and Primary Biological Evaluation of Triazole‐Modified Picroside II Compounds

“…For the synthesis of triazole, many scholars have tried various synthetic methods and obtained different experimental yields. At present, the main synthesis methods of triazole are as follows: one is the substrate alkynylated firstly and then reacted with the azide compounds, [23–25] the other is the substrate azided firstly and then reacted with the alkynyl group [26–33] . Besides, when Marepu et al [34] .…”

“…The action of sodium nitrite promotes the synthesis of triazole from imines and amine groups. Silalai et al [33] . also used iridoids as substrates, but unlike our research, the study first removed the glucose ring in the geniposide, and only carried out the structure on the iridoids modification means that there is no problem of modifying a single hydroxyl group when multiple hydroxyl groups exist at the same time.…”