<p>Herein, Vilsmeier reaction-based synthesized 1H-indole-3-carbaldehyde was utilized in the azines derivatives (<b>6a-d)</b> synthesis through C-5 halogen-substituted oxindoles and their anticancer effect against human cancer cells, as reported. The effect of halogens at C-5 of synthesized compounds (<b>6a-d</b>) on human cancer cells was demonstrated by the National Cancer Institute-Developmental Therapeutics Program, USA. The effect of halogens was notably cytotoxicity against cells, but the bromo-substituted compound <b>6c</b> was further analyzed under five-dose screening at different concentrations, including 10⁻⁴, 10⁻⁶, 10⁻⁵, 10⁻⁷, and 10⁻⁸M. It was concluded that EKVX and UACC-257 cell lines were shown to be −6.58 (lowest) and −4.65 (highest) GI₅₀ at log₁₀ high concentration −4.0, respectively. However, TGI values for RXF and UACC-257 cell lines were shown to be −5.12 (lowest) and −4.0 (more than) at the same concentrations. The lowest LC₅₀ value was calculated at −4.50 for RXF 393 cell line, while the highest LC₅₀ value was noted at less than −4.0 for the T-47D cell of breast cancer at log₁₀ high concentration −4.0, respectively. The aim of research is to demonstrate the halogen’s effects on human cancer cells whenever it is attached at a suitable position at C-5 of the oxindole ring. In the future it could be used as lead molecule in clinical in-vivo investigations on human lung cancer.</p><p></p>