Biological evaluation of the novel 3,3'-((4-nitrophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) derivative as potential anticancer agents via the selective induction of reactive oxygen species-mediated apoptosis.

Selective initiation of programmed cell death in cancer cells than normal cells is reflected as an attractive chemotherapeutic strategy. In the current study, a series of synthetic bis-coumarin derivatives were synthesized possessing reactive oxygen species (ROS) modulating functional groups and examined in four cancerous and two normal cell lines for their cytotoxic ability using MTT assay. Among these compounds, 3 l emerged as the most promising derivative in persuading apoptosis in human renal carcinoma cells (SKRC-45) among diverse cancer cell lines. 3 l causes significantly less cytotoxicity to normal kidney cells compared to cisplatin. This compound was able to induce apoptosis and cell-cycle arrest by modulating the p53 mediated apoptotic pathways via the generation of ROS, decreasing mitochondrial membrane potential, and causing DNA fragmentation. Unlike cisplatin, the 3 l derivative was found to inhibit the nuclear localisation of NF-κB in SKRC-45 cells. It was also found to reduce the proliferation, survival and migration ability of SKRC-45 cells by downregulating COX-2/ PTGES2 cascade and MMP-2. In an in vivo tumor model, 3 l showed an anticancer effect by reducing the mean tumor mass, volume and inducing caspase-3 activation, without affecting kidney function. Further studies are needed to establish 3 l as a promising anti-cancer drug candidate.

Amelioration of oxidative stress mediated inflammation and apoptosis in pancreatic islets by Lupeol in STZ-induced hyperglycaemic mice.

BACKGROUND: Type 1 Diabetes mellitus initiates by loss of pancreatic activity which affects other major organs leading to multi-organ failure. Lupeol, a novel phytochemical, is emerging as a potent bioactive molecule. However, the effect of lupeol on hyperglycaemia is not clearly understood. This study delivers an elaborate vision towards the detailed molecular pathway of lupeol against STZ induced diabetic difficulties of the pancreas. METHOD: The current experiments were designed to focus on the ameliorative effect of the triterpene in combating oxidative damage on the pancreas in a preclinical streptozotocin induced mouse model. After diabetic induction, the animals were subjected to administration with 75 mg kg-1 body weight of lupeol, thrice a week for 7 weeks. Histological measurements were done to investigate the anatomy of the pancreas as well as molecular mechanisms were explored. RESULTS: The compound was found to regulate several hyperglycaemic and oxidative stress related markers. Lupeol treatment also reversed the expression levels of inflammatory cytokines (TNF-α and IL-1ß) as well as attenuated the NF-κB mediated inflammatory and extrinsic apoptotic pathway. DISCUSSION: These findings in preclinical streptozotocin induced in vivo mouse model strongly suggest the discovery of novel properties of lupeol against oxidative stress in pancreatic ß cells by regulating the NF-κB and extrinsic apoptotic pathway.

Visible-Light-Promoted Intramolecular C-O Bond Formation via Csp3-H Functionalization: A Straightforward Synthetic Route to Biorelevant Dihydrofuro[3,2-c]chromenone Derivatives.

A photochemical method for the synthesis of functionalized dihydrofuro[3,2-c]chromenones via intramolecular Csp3-H cross-dehydrogenative oxygenation within a warfarin framework has been unearthed. Advantages of this protocol include abundant sunlight or low-energy visible light as the energy source, mild reaction conditions, and avoidance of metal catalysts.

Lupeol alters viability of SK-RC-45 (Renal cell carcinoma cell line) by modulating its mitochondrial dynamics.

Renal cell carcinoma (RCC) is the most common kidney cancer leading to 140,000 deaths per year. Among all RCCs 80% evolve from the epithelial proximal tubular cells within the kidney. There is a high tendency of developing chemoresistance and resistance to radiation therapy in most RCC patients. Therefore, kidney resection is considered as the most effective treatments for patients having localized RCC. There is a high tendency of post-operative recurrence among 20-40% of the patients and this recurrence is not curable. It is also clear that modern medicine has no curative treatment options against metastatic RCC. Lupeol [lup-20(29)-en-3ß-ol] is a pentacyclic triterpenoid compound naturally found in various edible fruits and in many traditionally used medicinal plants, and has been demonstrated as effective against highly metastatic melanoma and prostate cancers. The present study was designed to evaluate the effect of lupeol to RCC with molecular details. Treatment with lupeol on SK-RC-45 (a RCC cell line) with the LC50 dose of 40µM (for 48 h) induces mitochondrial hyper fission which eventually leads to apoptosis while SK-RC-45 counteracts by enhancing autophagy-mediated selective removal of fragmented mitochondria. This is the first study which concurrently reports the effects of lupeol on RCC and its effect on the mitochondrial dynamics of a cell. Herein, we conclude that lupeol has potential to be an effective agent against RCC with the modulation of mitochondrial dynamics.

Sopherone A and B: Two new biologically relevant dibenzo-α-pyrones from Cassia sophera.

Sopherone A (1) and B (2), two new biologically relevant dibenzo-α-pyrones, were isolated from the stems of Cassia sophera Linn. (Caesalpiniaceae). Their structures were elucidated by detailed analysis of their spectroscopic data, including 1D and 2D NMR.