Biologically Active α-Amino Amide Analogs and γδ T Cells-A Unique Anticancer Approach for Leukemia

Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active alpha-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (alpha-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (alpha-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC50 values of alpha-AAA-A and alpha-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of gamma delta T cells alone or in combination with alpha-AAA-A or alpha-AAA-B. Synthesized biologically active molecule alpha-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with alpha-AAA-B (44% and 36% respectively). Similarly, alpha-AAA-A showed low IC50 values for HL-60 (1.61 +/- 0.11 mu M) and K562 (3.01 +/- 0.14 mu M) compared to alpha-AAA-B (3.12 +/- 0.15 mu M and 6.21 & PLUSMN; 0.17 mu M respectively). Additive effect of amide analogs and gamma delta T cells showed significantly high leukemia cancer cell killing as compared to gamma delta T cells alone. A unique combinational therapy with gamma delta T cells and biologically active anti-cancer molecules (alpha-AAA-A/B), concomitantly may be a promising cancer therapy.

Automated summary

Advanced stage cancers pose challenges to mono-therapeutics, leading to low patient survival rates. This study explores a novel combinational therapy using biologically active alpha-amino amide analogs to increase cytotoxicity against leukemia cells, especially when combined with gamma delta T cells. This unique approach may offer promising potential for cancer therapy.