Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of an available structurally diverse antifungal drug armamentarium. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro anticandidal activities of globospiramine against two clinically relevant Candida species (C. albicans and C. tropicalis) and the exploration of its possible target proteins using in silico methods. Thus, the colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid along with a decrease in the number of viable CFUs by almost 50% at 60 min after treatment. The results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 8 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed well with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments suggested globospiramine to bind strongly with 1,3-β-glucan synthase and Als3 adhesin-enzymes indirectly involved in apoptosis-driven candidal inhibition.

A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.

A dimeric indole alkaloid, isovincathicine consisting of an aspidosperma type and modified iboga with C-7-C-20 connection type skeletons was first isolated from Catharanthus roseus, and the structure including stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Isovincathicine inhibited cell proliferation in A549 cells. We investigated the detailed mode of action of isovincathicine-induced inhibitory effects on cell proliferation in A549 cells. Flow cytometric analysis showed that isovincathicine-treated cells accumulated in the G2 phase after 24 h, and the percentage of cells showing cell death increased after 48 h. Western blotting also showed increased expression of BimEL, an apoptosis-related protein, and decreased expression of Mcl-1 and Bcl-xL. Isovincathicine was suggested to induce apoptosis in A549 cells by a mechanism is similar to that of vinblastine.

Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise structures and broad biological activities, which make them an important leading skeleton in the creation of new pesticides. In this work, we synthesized bisindole alkaloid barakacin in a simple seven-step process, and simultaneously designed and synthesized a series of its derivatives. Biological activity research indicated that most of these compounds displayed good antiviral activities against tobacco mosaic virus (TMV). Among them, compound 14b exerted a superior inhibitory effect in comparison to commercially available antiviral agent ribavirin, and could be expected to become a novel antiviral candidate. Molecular biology experiments and molecular docking research found that the potential target of compound 14b was TMV coat protein (CP). These compounds also showed broad-spectrum anti-fungal activities against seven kinds of plant fungi.

Indirubin is the crucial ingredient of Danggui Longhui Wan and Qing-Dai, traditional Chinese medicine herbal formulas used for the therapy of chronic myelocytic leukemia in China for hundreds of years. Although the monomeric indirubin has been used in China for the treatment human chronic myelocytic leukemia. However, due to low water solubility, poor pharmacokinetic properties and low therapeutic effects are the major obstacle, and had significantly limited its clinical application. Consequently, the attractive anticancer profile of indirubin has enthused numerous researchers to discover novel indirubin derivatives with improved pharmacodynamic activity as well as good pharmacokinetic property. In this paper, we comprehensively review the recent progress of anticancer potential of indirubins, structural modification and structure-activity relationship, which may provide useful direction for the further development of novel indirubins with improved pharmacological profiles for the treatment of various types of cancer.

Two new bisindole alkaloids, bisnaecarpamines A (1) and B (2), possessing a vobasine-sarpagine type skeleton were isolated from the bark of Tabernaemontana macrocarpa Jack. Their structures were elucidated by extensive spectroscopic methods and chemical correlation. The absolute configurations of compounds 1 and 2 were established using TDDFT-ECD calculation of the selected isomers. Bisnaecarpamine A exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 28.8 µM.

Caulerpin is a bisindolic alkaloid that has been obtained from many species of the genus Caulerpa. The main objective of this paper is to evaluate four extraction methods of caulerpin in the C. racemosa: maceration (DMA), Soxhlet extraction (SOX), ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The methods were compared through caulerpin content quantified by Ultraviolet-visible (UV-vis) spectrophotometry. The highest extract yield was obtained by SOX but the highest contain of caulerpin was presented in the MAE extract. The caulerpin content was significant different within the extacts by MAE and UAE, it yielded by MAE more than three times as much as UAE. The most efficient caulerpin extraction method had the parameters solvent, temperature and time optimised. Thus, the best conditions were achieved with MAE in ethanol during 7 min at 90 °C. Therefore, this work suggests an improved routine analysis of caulerpin by the green chemistry concept.

As part of an ongoing program to identify new bioactive compounds from Irish marine bioresources, we selected the subtidal sponge Spongosorites calcicola for chemical study, as fractions of this species displayed interesting cytotoxic bioactivities and chemical profiles. The first chemical investigation of this marine species led to the discovery of two new bisindole alkaloids of the topsentin family, together with six other known indole alkaloids. Missing the usual central core featured by the representatives of these marine natural products, the new metabolites may represent key biosynthetic intermediates for other known bisindoles. These compounds were found to exhibit weak cytotoxic activity against HeLa tumour cells, suggesting a specificity towards previously screened carcinoma and leukaemia cells.

Two new bisindole alkaloids, leucophyllinines A (1) and B (2) consisting of eburnane and quebrachamine-type skeletons were isolated from the bark of Leuconotis eugeniifolia, and their structures were elucidated on the basis of spectroscopic data. Leucophyllinines A and B showed antiplasmodial activities against Plasmodium falciparum 3D7.

A new bisindole alkaloid, melosuavine I (1) possessing an aspidosperma-aspidosperma dimeric skeleton, was isolated from the leaves of Melodinus suaveolens. The structure with absolute configuration of 1 was elucidated by a combination of MS, NMR and computational methods. MTT assays indicated that 1 exhibited significant cytotoxicity on human breast cancer BT549 cells with an IC50 value of 0.89 μM. Further study showed that 1 inhibited BT549 cell proliferation by inducing apoptosis through activation of caspase 3 and p53, and down-regulation of Bcl-2.