Novel substituted chromenopyridones (3a–j and 6a–d) were synthesized and evaluated in vitro for the cytotoxic activity against various human cancer cell lines such as prostate (PC-3), breast (MCF-7), CNS (IMR-32), cervix (Hela), and liver (Hep-G2). preliminary cytotoxic screening showed that all the compounds possess a good to moderate inhibitory activity against various cancer cell lines. Particularly, compound 6b bearing allyl moiety displayed a significant cytotoxic potential in comparison to standard drugs. 1. Introduction Cancer is the most dreaded group of diseases in which abnormal cells divide aggressively without control invade and spread to other parts of the body through the blood and lymph systems [1]. Despite tremendous advancements both in early diagnosis and approaches to treatment, cancer still remains an unconquered problem [1]. The development of new chemotherapeutic agents for the treatment of cancer with fewer side effects is an important goal for medicinal chemists. Heterocyclic compounds display a high degree of structural diversity and constitute the largest, most varied family of organic compounds evaluated for anticancer potential in past decades [2]. A perusal of the literature revealed that chromone framework constitutes an integral part of several natural products and biologically active molecules. Chromone derivatives exhibit a remarkable spectrum of pharmacological activities including antitumor [3], anti-inflammatory [4], antibacterial [5], antifungal [6], antioxidant [7], anti-HIV [8], vasodilator [9], antiviral [10], and antiallergenic [11]. Naturally occurring chromone based molecule, morusin, isolated from a Chinese herb, has been reported to be a potent antitumor agent [12]. Recently, we have developed some chromone based compounds such as substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-one and substituted 4-oxo-4H-chromene-3-carbothioic acid N-phenylthioamide, which display a promising cytotoxic activity against a number of human cancer cell lines [13]. Derivatives of 6-chloro-/fluorochromone have also been reported as potential topoisomerase inhibitor anticancer agents [14]. 2-Pyridone moiety is another substructural unit of several natural and synthetic molecules exhibiting diverse biological activities such as antitumor [15, 16], antimicrobial [17], anti-inflammatory [18], antiviral [19], and so forth. For instance, camptothecin, isolated from Camptotheca acuminate [20], is a naturally occurring DNA topoisomerase I poison possessing a pyridone nucleus. Due to a remarkable antiproliferative activity of
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