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Background: The synthesis of novel heterocyclic scaffolds with amide functionality is a key research area due to their plethora of medicinal applications. The present study aims to explore the synthesis of new cinnamido linked quinazolinone congeners and their potential as anticancer agents. Methods: Cytotoxicity evaluation, Cell cycle analysis, JC-1 staining, ROS, Annexin V assays, AO/EB, DAPI nuclear staining, Colony-forming assay and Western blot analysis. Results: Among the synthesized compounds, 5eb and 5fc have shown promising cytotoxic activity with an IC50 value of 3.89±1.01µM and 4.05±0.62µM against HeLa cell lines. The flow-cytometry analysis demonstrated that the compound 5eb arrested the sub-G1 phase of the cell cycle and induced apoptosis. Furthermore, the compound 5eb triggered the collapse of mitochondrial membrane potential (ΔΨm), which was assessed by JC-1 staining and also induced the generation of Reactive Oxygen Species. An increase in the expression of proapoptotic proteins such as Bax, p53, cleaved PARP and cleaved caspase-3 by 5eb confirmed the activation of the mitochondrial-dependent intrinsic apoptosis pathway. Conclusion: Our results suggest that compound 5eb and 5fc of cinnamido linked quinazolinone derivatives could serve as potential leads in the development of novel chemotherapeutic agents.

An efficient, metal-free approach to access pyrazolo-[1,5-c]quinazolines with 3-ylideneoxindoles and tosyldiazomethane (TsDAM) under mild aqueous reaction conditions has been developed and the solvent involvement in the present reaction has also been explored for the first time. This greener approach involves 1,3-dipolar cycloaddition, regioselective ring expansion, followed by the elimination of tosyl group with aqueous base in a single operation, and the product can be isolated in high purity without column chromatographic separation. The method is also compatible with a large variety of functional groups, providing good to excellent yields in water, thus resulting in a decrease of environmental impact in the pharmaceutical industry.

An efficient molecular iodine-catalysed one-pot strategy has been accomplished for the construction of various fused heterocycles such as pyridoimidazoles, pyrrolo[1,2-a]quinoxalines and imidazobenzothiazoles under metal and oxidant free conditions. Gratifyingly, this method allows the sequential formation of C–N and C–C bonds with concomitant CO–C(alkyl) bond cleavage. The key features of this protocol are a broad substrate scope, operational simplicity, good to moderate yields and metal-free conditions, which make this protocol convenient for the generation of a library of fused polyheterocycles.

A series of new podophyllotoxin linked β-carboline congeners have been synthesized by coupling various substituted β-carboline acids with 4β-aminopodophyllotoxin. Evaluation of their anticancer activity against a panel of human cancer cell lines such as lung cancer (A549), prostate cancer (DU-145), MDA MB-231 (breast cancer), HT-29 (colon cancer) and HeLa (cervical cancer) suggested that 7i and 7j are the most cytotoxic compounds with IC50 values of 1.07 ± 0.07 μM and 1.14 ± 0.16 respectively against DU-145 cell line. Further, detailed biological studies such as cell cycle analysis, topoisomerase II inhibition, Comet assay, DNA binding studies and docking studies have revealed that these congeners are DNA interacting topoisomerase II inhibitors.

A facile and efficient metal-free, one-pot, three component synthetic protocol has been developed for the synthesis of medicinally important substituted imidazo[1,2-a]pyridines via the iodine-catalysed oxidative amination of benzylic C–H bonds of azaarenes with 2-aminoazines and condensation with isocyanides. The presented methodology offers the advantages of wide substrate scope, moderate reaction conditions, environment friendliness, clean and simple protocol with high atom economy apart from higher yields. The synthesized compounds were screened for their anti-cancer activity in selected human cancer cell lines. Compounds 4a, 4b, 4c, 4i, 7a, 7b and 7m have significant IC50 values ranging from 4.88 ± 0.28 to 14.55 ± 0.74 μM.

An efficient, operationally simple and one-pot multi-component approach has been developed for the construction of pyrazolyl-thiazoles using sulfamic acid (H2NSO3H) as a green catalyst in water. The notable features of this protocol include mild reaction conditions, enhanced selectivity with good yields and wide substrate scope, which makes it an attractive and useful process for the synthesis of biologically important newer pyrazolyl-thiazole compounds. A series of compounds (4a–z) were synthesized and also evaluated for their cytotoxic activity against three human cancer cell lines. Among them, 4b, 4c and 4e exhibited considerable cytotoxicity with an IC50 value of < 5 μM.

An operationally facile and high yielding one-pot, three-component protocol has been developed for the preparation of selectively trans-2,3-dihydrofuro[3,2-c]coumarins and trans-1,2-dihydrobenzo[h]furo[3,2-c]quinolinones. This protocol proceeds through a domino Knoevenagel condensation, a Michael addition followed by intramolecular SN2 cyclisation. All the synthesized compounds have been evaluated for their in vitro cytotoxic activity against selected human cancer cell lines. Interestingly, most of the compounds have exhibited considerable cytotoxicity with IC50 values

An efficient metal-free, one-pot protocol was developed for the synthesis of variety benzimidazole and quinazolinones in moderate to good yields. This protocol proceeds via oxidation of benzylamine, resulting in in-situ aldehyde formation followed by the condensation with o-phenylenediamine and o-aminobenzamide to the corresponding N-heterocycles using a mild oxidant phenyliodonium diacetate (PIDA). We describe a new strategy for C–N bond cleavage and formation in the absence of transition-metal reagent or ligand under environmentally benign reaction conditions.

A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3- O-methyl viridicatin and their scale up.