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An iboga‐vobasine bisindole alkaloid, 16′‐decarbomethoxydihydrovoacamine (1) isolated from the stem bark extract of Tabernaemontana corymbosa exhibited strong cytotoxicity against colorectal cancer cell lines in our preliminary study. As an initial step to elucidate its anti‐proliferative mechanism, the DNA binding and topoisomerase I (topo1) inhibitory activities of the bisindole 1 were investigated. The results of the in vitro DNA binding studies and molecular docking calculations collectively suggested that 1 binds to the DNA minor groove via hydrophobic interactions with a binding constant (Kb) of 7.40×105 M−1. Treatment of Escherichia coli topo1 with 1 did not inhibit the enzyme from relaxing the supercoiled plasmid DNA pBR322, indicating that the cytotoxicity of 1 in colorectal cancer cells is independent of topo1. The bisindole is predicted to possess substantial bioavailability without major toxicity. Moreover, the cytotoxicity of 1 is selective towards the colorectal cancer cells as evaluated using the MTT assay.

Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.