DataSheet_1_Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia.pdf

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 α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC50 values of α-AAA-A and α-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 γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC50 values for HL-60 (1.61 ± 0.11 μM) and K562 (3.01 ± 0.14 μM) compared to α-AAA-B (3.12 ± 0.15 μM and 6.21 ± 0.17 μM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy.

晚期癌症侵袭性强，单药疗法（mono-therapeutics）难以实现有效治疗，会大幅降低患者生存率。因此，亟需开发兼具更高效价与疗效的独特治疗策略。本研究探索了一种新型强效联合疗法（combinational therapy）用于治疗晚期白血病。本研究通过线性Ugi多组分反应（Ugi multicomponent reaction）合成了两种生物活性α-酰胺类似物（α-amino amide analogs）：(RS)-N-(2-(环己基氨基)-2-氧代-1-苯乙基)-N-苯基丙炔酰胺（α-AAA-A）与(RS)-N-(2-(环己基氨基)-2-氧代-1-苯乙基)-N-苯基丁-2-烯酰胺（α-AAA-B）。采用MTT法（MTT assay）分析了α-AAA-A与α-AAA-B对白血病细胞系HL-60及K562的细胞毒性及半抑制浓度（IC50）。此外，本研究还通过细胞毒性实验，探究了单独使用γδ T细胞（γδ T cells），或联合α-AAA-A/α-AAA-B时，对白血病细胞系的杀伤百分比。实验结果显示，相较于α-AAA-B（对HL-60与K562的杀伤率分别为44%与36%），α-AAA-A对两种细胞系的杀伤效果更优，分别可达54%与44%。同样，α-AAA-B对HL-60的半抑制浓度为3.12±0.15 μM，对K562为6.21±0.17 μM；而α-AAA-A的半抑制浓度更低，分别为1.61±0.11 μM与3.01±0.14 μM。进一步分析发现，α-酰胺类似物与γδ T细胞的相加效应，可显著提升白血病癌细胞的杀伤效果，优于单独使用γδ T细胞的治疗效果。综上，γδ T细胞与抗癌活性分子α-AAA-A/B联合使用的独特治疗策略，有望成为极具前景的癌症治疗方案。