Cancer is characterized by an abnormal growth of the cells in an uncontrolled manner. These cells have the potential to invade and can eventually turn into malignancy, leading to highly fatal forms of tumor. Small subpopulations of cancer cells that are long-lived with the potential of excessive self-renewal and tumor formation are called cancer stem cells (CSCs) or cancer-initiating cells or tumor stem cells. CSCs can be found in tissues, such as breast, brain, lung, liver, ovary, and testis; however, their origin is still a matter of debate. These cells can differentiate and possess self-renewal capacity maintained by numerous intracellular signal transduction pathways, such as the Wnt/β-catenin signaling, Notch signaling, transforming growth factor-β signaling, and Hedgehog signaling. They can also contribute to numerous malignancies and are an important reason for tumor recurrence and metastasis because they are resistant to the known therapeutic strategies that mainly target the bulk of the tumor cells. This review contains collected and compiled information after analyzing published works of the last three decades. The goal was to gather information of recent breakthroughs related to CSCs, strategies to target CSCs’ niche (e.g., nanotechnology with tumor biology), and their signaling pathways for cancer therapy. Moreover, the role of metformin, an antidiabetic drug, acting as a chemotherapeutic agent on CSCs by inhibiting cellular transformation and its selective killing is also addressed.
An efficient domino approach for the synthesis of pyrrolobenzoxazine derivatives is described. The FeCl-promoted domino reaction between aroylmethylidene malonates and benzoxazinones has been successfully established to afford the title compounds in good to excellent yield under mild reaction conditions. The domino protocol provides a concise and straightforward access to highly substituted pyrrolobenzoxazines with high efficiency and excellent functional group tolerance.
An efficient [3 + 2]/[4 + 2] or double [4 + 2] cycloaddition strategy has been established for the synthesis of heterocyclic systems under mild conditions. The reaction pathway is governed by the nature of reaction partner. Several dihydrofurocoumarin, furopyranocoumarin, dihydrofuran, dihydrobenzopyran, and dihydrobenzofuran derivatives were obtained as single diastereomers from cyclic or acyclic enol ethers and styrenes. This one-pot transformation constructed C-C and C-O bonds and generated molecular complexity by domino/tandem process to produce the heterocyclic systems in good yields. The ring closure of domino protocol was highly stereoselective and resulted in the formation of cis-fused systems.
The synthesis of substituted 3-isoxazolethioethers and their bioevaluation as anti-leishmanial and anti-bacterial agents are described. The DBU-catalyzed thioetherification of substituted 3-nitroisoxazoles via nucleophilic aromatic substitution (S N Ar) reaction using aromatic, aliphatic and heteroaromatic thiols gave the title compounds in good yields. These 3-thioisoxazole derivatives were synthetically modified to prepare new com- ,4]thiazepin-4(5H)-ones. Four compounds displayed promising activity against amastigote stage of L. donovani whereas two compounds displayed good antibacterial effect.
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