Month 2018 Design, Synthesis and SAR Study of Novel Spiro [Pyrimido[5,4-b]Quin- oline-10,5 0 -Pyrrolo[2,3-d]Pyrimidine] Derivatives as Promising Anticancer Agents Asha V. Chate, a Sagar P. Kamdi, a Amruta N. Bhagat, a Chetan K. Jadhav, a Amol Nipte, a Aniket P. Sarkate, b Shailee V. Tiwari, c and Charansingh H. Gill a * a Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra 431004, India b Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra 431004, India c Y.B. Chavan College of Pharmacy, Razabaug, Aurangabad, Maharashtra 431001, India *E-mail: chgill16@gmail.com Received February 9, 2018 DOI 10.1002/jhet.3286 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com). Novel spiro [pyrimido[5,4-b]quinoline-10,5 0 -pyrrolo[2,3-d]pyrimidine] derivatives were designed and synthesized, and their chemical structures were confirmed by IR, NMR, elemental analysis, and mass spec- tral analysis. The anticancer activities of the newly synthesized compounds were evaluated in vitro against four human cancer cell lines including A431, PC-3, MCF-7, and MCF-10A by MTT assay. The screening results showed that three compounds (4m, 4q, and 4s) exhibited potent cytotoxic activities with IC 50 values between 7.82 and 9.88 μM against human breast cancer cell line (MCF-7). Further in vitro studies revealed that inhibition of Sunitinib could be the possible mechanism of action of these molecules. J. Heterocyclic Chem., 00, 00 (2018). INTRODUCTION Development of novel anticancer therapeutic candidates is one of the key challenges that remain still in medicinal chemistry. Cancer is one of the main diseases that poses a direct threat to human health and life. Cancer, in which a group of cells play relentless growth and spread to distant sites in the body, is the challenging disorder in the present scenario leading to morbidity and mortality across the globe [1]. Most anticancer drugs inhibit the proliferation of cancer cells through inducing apoptosis [2]. Approximately 7 million people die from cancer every year, and this number is growing rapidly [3]. According to WHO estimates, 8.2 million cancer deaths were registered in 2012 and is expected to rise to 13.1 million by 2030 [4]. The lung, bronchus, prostate, and colorectal continue to be the most common causes of cancer, and life ends in death [5]. The developing populations affected by the numbers of different types of cancer in Africa, Asia, and Central and South America account for more than 60% of the world’s total cancer cases and about 70% of the world’s cancer deaths [6]. In 2025, the estimated death from all can- cer types is about 80% throughout the globe [7]. A cancer is an uncontrolled growth of a single cell having inherent proliferation property [8]. At present, a wide range of cytotoxic drugs are in queue by utilizing, alone or in combination, to treat different cancer and cancer stages. In addition, several drugs are already in different phases of clinical trials to treat various types of cancers. Some of these drugs showed cytotoxic nature, and they are not able to discriminate cancerous and normal cell types at any more; consequently, they are involved in serious side effects. The current anticancer drugs in clinical trials showed unnecessary organ toxicity, short circulating half-life, lack of cell specificity, angiogenesis, and also noticeable that they have tendency to induce resistance [9] in target cells [10]. Hence, to save the millions lives around the globe, continuous efforts needed to develop target anticancer drug-like candidates with minimal side effects. Considering this fact, to design drugs that specifically target cancer cells is a major challenge. In the search for prospective anticancer agents, considerable effort has been made on the development of heterocyclic motifs based on their structural design. It is worth noting that isatin (indolin-2,3-dione), a “privileged © 2018 Wiley Periodicals, Inc.