Semisynthetic derivatives of haemanthamine and their in vitro antiproliferative activity evaluation against a panel of human cell lines

In this study, a new series of aliphatic, cyclic, and heterocyclic derivatives of haeman-thamine was designed and synthesized to enhance its inhibitory effect on the proliferation and viability of cancer cells. A library of haemanthamine derivatives was subjected to 10 lM single-dose cytotoxicity screening against a panel of human cell lines of various histotypes. Initial cytotoxicity evaluation of the parent haemanthamine (1) and a series of twenty-nine (2-30) semisynthetic analogues showed that for some of the newly formed derivatives, a certain cytotoxic effect was observed, in one case even higher than that of the parent compound. Specifically, 11-O-(4-chlor o-3-nitrobenzoyl)haemanthamine (21) showed an enhanced antiproliferative effect, where the mean growth percent (GP) value was 5% compared to haemanthamine, leading to a decrease in the GP to 25%. Among ten cell lines tested, derivative 21, bearing a substituted aromatic ester bond via C-11 of haemanthamine, had excellent activity for inhibiting the growth of HeLa (IC50 = 0.2 & nbsp;+/-& nbsp;0.1 mu M), A549 (IC50 = 1.7 & nbsp;+/- 0.1 mu M) and HT-29 (IC50 = 2.2 & nbsp;+/- 0.1 mu M) cells. When evaluating response kinetics, we found that 21 and haemanthamine dose-and time-dependently suppressed the proliferation of A549 cells. In contrast to haemanthamine (1), Trypan blue and lactate dehydrogenase (LDH) release assay revealed that 21 was capable of reducing the survival of A549 cells. (C)& nbsp;2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.& nbsp;

Automated summary

A new series of haemanthamine derivatives were designed and synthesized to enhance inhibitory effect on cancer cell proliferation and viability. Among them, derivative 21 showed enhanced antiproliferative effect, especially on HeLa, A549, and HT-29 cell lines. The cytotoxicity of derivative 21 was dose- and time-dependently suppressing cell proliferation and reducing cell survival compared to haemanthamine.