K.S.R. Pai

Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one (4a–o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, 1H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.

Some new indole–coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies

Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole-coumarin hybrids - 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability.

Anticancer activity of Berberis aristata in Ehrlich ascites carcinoma-bearing mice: A preliminary study

Context: Berberis aristata DC (Berberidaceae) is an important medicinal plant with claims of widespread medicinal value in indigenous medicine. It is used by herbal healers to treat oral cancers. Objective: To evaluate the antineoplastic activity of the extracts of Berberis aristata in Ehrlich ascites carcinoma (EAC)-bearing mice with cisplatin as positive control in the advanced stage of tumorigenesis. Materials and methods: Brine shrimp lethality bioassay (BSL) of extracts and effect on the tumor cell viability in vitro were carried out. EAC was induced in Swiss albino mice by injecting 106 cell/mL of tumor cell suspension i.p. Antineoplastic activity of the aqueous and ethanol extracts (100 and 6.5 mg/kg i.p., respectively) was compared with that of cisplatin (3.5 mg/kg i.p.) on the parameters such as percentage increase in weight, median survival time, and hematology. Results: Ethanol extract attenuated percentage increase in weight gain (−6.86 ± 1.50) due to tumor cell proliferation and increased the survival time (19.5 days) when compared to control group (19.10 ± 2.31 and 16 days, respectively). However, the effect was less than that of cisplatin. In vitro cytotoxicity assay as well as BSL test showed the cytotoxic effect of the extracts. Cisplatin and the extracts reversed the tumor-induced alterations in total white blood cell count, differential leukocyte counts, total red blood cell count, and hemoglobin contents. Discussion and conclusion: Of the two extracts, the ethanol extract was observed to be more efficient and the presence of alkaloids and flavonoids may be responsible for the observed anticancer effects.

Oxazepine Derivative as an Antitumor Agent and Snail1 Inhibitor against Human Colorectal Adenocarcinoma

Colorectal cancer is the third most common malignancy in man, with significant morbidity and mortality. Metastasis, the major cause of cancer-associated deaths occurs as a multistep process, where cancer cells detach from the primary tumor, intravasate circulation to disseminate and invade surrounding tissues to form the secondary tumors. The effectiveness of many anticancer drugs is limited by their toxicity to normal rapidly growing cells. Four oxazepines were synthesized by the cycloaddition reaction between schiff bases and maleic anhydride, which were characterized by CHN analysis and advanced spectral techniques. The cytotoxicity of oxazepines against HCT116 (human colon cancer) cell lines were studied using Sulphorhodamine-B (SRB) assay, and their antimigratory properties using wound healing assay. 1-[2-(2,3-dihydro-1H-indol-3-yl)-4,7-dioxo-4,7-dihydro-1,3-oxazepin-3(2H)- yl]thiourea (2b) exhibited very low IC50 in SRB assay with good antimigratory activity as observed in wound healing assay. Snail 1, a transcription regulator of E-cadherin induces epithelial-to mesenchymal transition, reduces intercellular adhesion and increases cell motility, endows epithelial cancer cells with migration and invasive properties. Snail1 is upregulated in several human cancers and is frequently associated with apoptotic resistance, invasiveness, metastases and poor prognosis and it can act as a molecular target in cancer treatment. The docking studies of 2b with the active site of snail1 suggest it to be a potent chemotherapeutic agent in the treatment of colorectal cancer