Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics.

由于化学治疗剂的微弱和次佳的治疗反应，或者由于癌细胞中自发的复杂多药耐药性的出现，癌症仍然被认为是全球主要的健康问题之一。这产生了对开发新的抗癌剂的持续需求。受到基于天然产物的药物开发的高成功率和当前研究场景的困扰，我们合成了一系列新的3,4,5-三甲氧基苯基环侧基含硫氰基嘧啶衍生物，并与不同的胺组成棍棒，旨在寻找抗癌的铅化合物。为了探索合成衍生物的抗增殖谱，体外美国国家癌症研究所（NCI）对60种癌细胞系进行了评估，这些细胞系代表了主要的癌症疾病类型。大多数衍生物显示出良好至中等的抗增殖活性。结果表明，化合物4e表现出最有前途的广谱抗癌活性，并且对代表多种癌症疾病的各种细胞系具有高生长抑制作用。化合物4e在人乳腺癌MDA-MB-231细胞中的机制研究表明，化合物4e通过诱导细胞凋亡触发细胞死亡。还进行了ADMET研究和反向筛选，以鉴定设计分子的潜在靶标。结论是3,4,5-三甲氧基苯基环侧基含硫氰基嘧啶衍生物4e可以作为有希望的分子，用于进一步开发新型抗癌治疗剂。