Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The biological result showed that those derivatives exhibited potent activities on inhibiting cancer cell growth, and the structure-activity relationships were investigated. Among them, compound 4g, which was protected by benzoyl group in 7-phenolic position and nitrified in 14-position, showed impressive inhibition on all 5 cancer cell lines, especially WM9 cell line, with an IC₅₀ value of 1.07 µM. Further mechanistic studies demonstrated that compound 4g may induce cancer cell death by apoptotic means. These research results suggested that compound 4g could be a lead for the further development toward an anticancer agent against human melanoma WM9 in the future.

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, “Drug Synthesis and Analysis,” meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

Hepatocellular carcinoma (HCC) remains a significant global health challenge, with drug therapy being a critical treatment approach. However, the development of drug resistance and the occurrence of adverse reactions to existing medications have made the creation of new HCC treatments urgent. Tetrandrine, a bisbenzylisoquinoline alkaloid from natural products, has shown great potential in this area. Yet, systematic comparative studies on different tetrandrine modification sites (such as C-7 and C-14) are lacking, which has hindered the simultaneous optimization of its antitumor activity and synthetic feasibility. In this study, we focused on a C-7 modification strategy and designed and synthesized 38 novel tetrandrine sulfonate derivatives (including 31 new compounds) through an efficient one-step reaction. The in vitro antiproliferative activities of these derivatives were evaluated against four HCC cell lines (HepG-2, SMMC-7721, SK-Hep-1, and QGY-7701), and a systematic comparison with previously reported C-14 sulfonate derivatives was conducted. The results showed that all the C-7 derivatives exhibited good antiproliferative activities against HCC. Notably, compound 15 demonstrated significant antiproliferative activity against all tested cell lines, with IC₅₀ values ranging from 3.28 to 6.16 µM, which is superior to the first-line clinical drug 5-fluorouracil. Mechanistic studies revealed that compound 15 exerts its antitumor effects by regulating the balance of Bcl-2 and Bax proteins, triggering the release of cytochrome C from mitochondria, and subsequently activating the caspase-3-dependent apoptosis pathway. The results of target prediction showed that PDGFRA, FLT1, PIK3CD and MET might be the main targets of compound 15 against hepatocellular carcinoma. Although C-14 sulfonate derivatives showed slightly higher in vitro activity, C-7 derivatives (particularly compound 15) exhibited significant advantages in synthetic efficiency (one-step reaction), ease of purification, environmental friendliness, and scalability for industrial production. In conclusion, this study has established C-7 sulfonation as an efficient strategy for developing tetrandrine-based anti-HCC agents. With its remarkable antitumor activity, excellent synthetic process characteristics, and clear apoptosis-inducing mechanism, compound 15 has emerged as a highly promising clinical candidate. This C-7 modification platform provides a viable path for transforming natural product derivatives into clinical therapies for HCC treatment.