Jessy Elizabeth Mathew

Synthesis of Spiroannulated Dihydrofurans by Cerium(IV) Ammonium Nitrate Mediated Addition Of 1,3-Dicarbonyl Compounds to Exocyclic Alkenes

Abstract Cerium (IV) ammonium nitrate (CAN) mediated addition of 1, 3-dicarbonyl compounds to exocyclic alkenes occurs smoothly at 5°C in methanol to afford spiroannulated dihydrofurans in moderate to good yields.

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

Abstract A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-aminothiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in the presence of dicyclohexylcarbodiimide afforded thiazolidin- 4-ones. All the compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by MTT assay. Most of the derivatives showed an IC50 less than 150 μmol L-1. Among the compounds tested, 2-(2-nitrophenyl)- 3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2- -yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3- -(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC50 values of 46.34, 66.84, and 60.71 μmol L-1, respectively. Antioxidant studies of all the synthesized compounds were carried out by diphenylpicrylhydrazyl (DPPH) assay. Among the compounds tested, 2-phenyl-3-(5-styryl- -1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC50 of 161.93 μmol L-1.

Synthesis and biological evaluation of novel pyrimidine-2(1H)-ones/thiones as potent anti-inflammatory and anticancer agents

Recently there has been an increased interest in the synthesis of pyrimidinone and their applications in medicinal chemistry. Pyrimidinone derivatives represent one of the active classes of the compounds possessing a wide spectrum of biological activities such as anti-tumour, anti-fungal, anti-inflammatory, anti-bacterial, etc. This study utilises chalcones as starting compounds that are obtained by Claisen-Schmidt condensation. These chalcones underwent cyclisation upon treatment with urea and thiourea in the presence of sodium hydroxide to obtain the corresponding pyrimidinones and pyrimidinethiones. The structures of the synthesized compounds were investigated by means of UV, IR, 1H NMR and Mass spectral analysis. The anti-oxidant activity of the compounds was measured by standard free radical scavenging assays (DPPH, Nitric oxide radicals). The compounds with significant anti-oxidant activity were then screened for the in vivo anti-inflammatory activity and it showed that the compounds ETT and DMT possess good activity as comparable to the standard. All the synthesized compounds were evaluated for their in vitro anti-cancer activity by MTT assay among which compounds CLU and ETU showed significant activity against HeLa and HepG2 cell lines, respectively.

OXIDATIVE ADDITION OF 1,3-DICARBONYL COMPOUNDS TO ALKENES MEDIATED BY CERIUM(IV) AMMONIUM NITRATE AND MANGANESE(III) ACETATE : A COMPARATIVE STUDY

The oxidative addition of dimedone, acetylacetone and ethyl acetoacetate to cyclic and acyclic alkenes mediated by CAN gives dihydrofurans in good yields. Similar addition of the radical generated from dimethyl malonate to alkenes provides lactones. A comparative study of these reactions vis-a-vis those mediated by Mn(OAc)3 has shown that the former generally lead to higher yields of products. The milder reaction conditions, experimental simplicity, and the solubility of CAN in common organic solvents like methanol, acetonitrile and THF are other advantages. Thus it appears from this study that CAN is superior to the commonly used Mn(OAc)3.

Effect of ethanol extract of Sphaeranthus indicus on cisplatin-induced nephrotoxicity in rats

Cisplatin is an anticancer drug extensively used against a variety of cancers. Cisplatin chemotherapy is found to manifest dose-dependent nephrotoxicity. Depletion of the renal antioxidant defence system has been suggested to be the main cause of cisplatin-induced nephrotoxicity. The purpose of this study is to investigate whether the ethanol extract of entire plant of Sphaeranthus indicus could reduce the intensity of toxicity in albino rats. Nephrotoxicity was assessed by determining the serum creatinine and urea levels and renal antioxidant status in rats after cisplatin administration (12 mg kg−1 body weight, i.p.). The ethanol extract of S. indicus (150 and 300 mg kg−1 body weight) was administered orally from the sixth day onwards for 10 days after cisplatin administration. The extract significantly reduced the elevated serum creatinine and urea levels. Renal antioxidant defence systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione level that are depleted by cisplatin therapy were restored to normal by treatment with the extract. Cisplatin-induced lipid peroxidation was also found to be markedly reduced by treatment with the extract. These results suggest that S. indicus has protective effect against cisplatin-induced nephrotoxicity, which may be attributed to its antioxidant potential.

Synthesis of novel class of 2-oxazolidinone based chiral ionic liquids

Abstract New class of chiral ionic liquids/ionic salts based on 2-oxazolidinone were designed and synthesized using a very simple method and in good yields. The properties of these compounds were studied. Graphical Abstract

Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK Cellular Signaling in HepG2 cells Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK Cellular Signaling in HepG2 cells

BACKGROUND Hepatocellular carcinoma (HCC) is the fifth leading cause of cáncer mortality. Elytranthe parasitica (L.) Danser (EP), a hemiparasitic plant (Loranthaceae) has potent anti-cancer properties. OBJECTIVE In the study, we investigated the effect of EP fractions on the expression of apoptosis and mitogenactivated protein kinase (MAPK) markers deregulated in HCC. Bioactivity fractionation was performed to isolate the phytochemical(s) exerting anti-tumor activity in HepG2 cells. METHOD Anti-proliferative, clonogenic and anti-metastatic effects of EP fractions were examined in hepatocellular carcinoma cell line, HepG2 by Sulphorhodamine B, colony formation and scratch wound assays respectively in hepatocellular cell line, HepG2. The effects of EP fractions on key markers of apoptosis and MAPK signaling pathways were explored. KEY FINDINGS EP bioactive fractions showed significant anti-tumor potential, reduced clonogenicity and considerably inhibited cell migration in HepG2 cells in vitro. The fractions augmented annexin V binding and induced apoptosis by causing cell cycle arrest at G2/M and S phase checkpoints. The fractions increased expression levels of p53, bad, cleaved PARP (Poly ADP ribose polymerase) and cleaved Caspase-3. Expression levels of phosphorylated ERK1/2 (Extracellular signal-regulated kinase) were downregulated. Pinocembrin-7-O-ß-D-glucoside and chrysin were isolated and characterized for the first time from Elytranthe parasitica (L.) Danser. CONCLUSION Our findings reveal that EP fractions induced cell cycle arrest and triggered apoptosis in HepG2 cells by upregulating apoptosis and deactivating MAPK pathway. It signifies that pinocembrin glycoside and chrysin are bioactive phytochemicals contributing to the potent anti-hepatocarcinoma effects on HepG2 cells. Hence, bioactive EP fractions could be used as a therapeutic agent for effective HCC therapy.

Identity-based High-performance thin Layer Chromatography Fingerprinting Profile and Tumor Inhibitory Potential of Anisochilus carnosus (L.f.) wall Against Ehrlich Ascites Carcinoma

Context: Anisochilus carnosus (L.f.) wall belonging to the family Lamiaceae is a plant that is widely used in folk medicine for treating eczema, cold, cough, and fever. Objective: In the present study, we explored the anticancer potential of A. carnosus leaves against Ehrlich ascites carcinoma (EAC) and estimated the quantity of luteolin present in various extracts and fractions of A. carnosus by high-performance thin layer chromatography (HPTLC) fingerprinting. Materials and Methods: Various factors such as tumor volume, tumor cell viability, tumor weight, prolongation of lifespan, and hematological parameters were assessed. Result: We observed a significant lowering in tumor volume, tumor weight, and cell viability in EAC-induced mice following intervention with A. carnosus extracts. Also, there was a considerable prolongation of host lifespan and restoration of hematological parameters to almost normal levels with A. carnosus treatment. HPTLC fingerprinting of various extracts and fractions of A. carnosus along with luteolin as the reference standard revealed the occurrence of luteolin in all tested extracts and fractions of A. carnosus with the highest concentration being reported in the ethanol fraction. Conclusion: A. carnosus exhibits potent anti-tumor potential which can most likely be attributed to the occurrence of different phytochemicals such as phytosterols, terpenoids, and flavonoids in the plant. Further studies to isolate compounds from A. carnosus and understand the mechanism of anti-tumor activity would be worthwhile. SUMMARY EAC induced mice that received A. carnosus treatment exhibited significant reduction in tumor volume, tumor weight and tumor cell viability. Their life span was considerably prolonged. We detected luteolin in A. carnosus aqueous and ethanol extract using HPTLC. Hence, anticancer activity of A. carnosus can be partly attributed to the presence of luteolin.