Evaluation of phenolic content and antioxidant potency in various parts of Cassia auriculata L.: a traditionally valued plant.

Presence of polyphenolic content in various part of the plant exhibit wide pharmacological activities including antioxidant activity. The present study was designed to evaluate the phenolic contents (total phenols, flavonoid and tannins) and antioxidant properties of ethanolic extracts of flower, leaf, pod, bark and root obtained from Cassia auriculata. Ethanolic extracts of various parts of C. auriculata obtained by sonication extraction techniques are studied for their phenolic contents and DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging assay as well as total antioxidant assays using UV visible spectrophotometer. Among the various parts of the plant studied, bark showed significant content of phenolics, flavonoids and tannins followed by the root, leaf, flower and pod. Even bark extract exhibited highest antioxidant capacity in DPPH assay followed by root, leaf, flower and pod with a value of 766.7, 679.3, 644.9, 572.5 and 474.7 mg vitamin C equivalent antioxidant capacity (mg VCEAC)/sample, respectively. In addition, mg VCEAC values obtained from the total antioxidant assay was in the increasing order of bark > root > leaf > flower > pod. Moreover, a strong correlation was also found between phenolic contents and antioxidant values indicating their influence in the found antioxidant activity, hence the bark extract can be employed as an ideal candidate for herbal based pharmaceutical product. Results of the present study also emphasize variation in the chemical composition as well as biological activity ensuring the importance of proper selection of particular part of the plant to evaluate their therapeutic potency.

Design of new drug molecules to be used in reversing multidrug resistance in cancer cells.

Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer cells and some have undergone clinical trials, but currently none are in clinical use. Unfortunately, most of these agents suffer clinically from their intrinsic toxicity or from undesired effects on the pharmacokinetics of the accompanying anti-cancer drugs. An acridonecarboxamide (GF120918), Imidazo acridone (C(1311)) and timethylene acridone derivative 1,3-bis(9-oxoacridin-10-yl)-propane (PBA) have already been shown to be among the group of compounds known to modify P-gp mediated MDR in cancer. In the recent past it has been identified that various N(10)-substituted acridones can reverse the multidrug resistance (MDR) in cancer by selectively inhibiting the multidrug resistance associated protein (MRP) and calmodulin dependent cyclic AMP phosphodiesterase. This article envisages the various drugs being developed for treating MDR in cancer cells and especially the acridone derivatives which are being developed by the author.

Chloro acridone derivatives as cytotoxic agents active on multidrug-resistant cell lines and their duplex DNA complex studies by electrospray ionization mass spectrometry.

We report herein in vitro anti-proliferative activity and duplex DNA complex studies of a series of N10-substituted acridone derivatives. All the molecules have been designed on the basis of the presence of specific recognition patterns consisting of hydrogen bond acceptors (or electron donors), carbonyl, chloro groups with precise spatial separation and structural features (lipophilicity, positive charge at neutral pH and presence of aromatic rings). The in vitro cytotoxic effects have been demonstrated against human promyelocytic leukemia sensitive cell line (HL-60), including its multidrug cross-resistance of two main (P-gp and MRP) phenotype sublines vincristine-resistant (HL-60/VINC) and doxorubicin-resistant (HL-60/DX) cancer cell lines. Compound 4 showed very good activity against sensitive and resistant cell lines. The noncovalent complexes of these molecules with DNA duplex has been investigated in gas phase by using a fast, robust and sensitive electrospray ionization mass spectrometry (ESI-MS) technique. Equilibrium association constants (K1) and percentage of intact complexes were determined. The combined results show that these acridone derivatives interact with DNA duplex by intercalation between the base pairs, possess higher affinity to GC than AT base pairs of the DNA and they could not interact noncovalently with the minor grooves of the DNA in solution-free gas phase. Examination of the relationship between lipophilicity and cytotoxic properties of acridone derivatives showed a poor correlation. The in vitro cytotoxic studies in resistant cancer cell lines of compound 4 showed that it might be a promising new hit for further development of anti-MDR agent.