S. C. Puri

Synthesis of 3,5‐Diphenyl‐1H‐Pyrazoles

Abstract An efficient and convenient synthesis of 3,5‐diphenyl‐1H‐pyrazoles from chalcones by the action of hydrazine hydrate on chalcone‐epoxide followed by simultaneous dehydration is reported.

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 μg ml−1. S1 exhibited 58.40 ± 0.8% inhibition (at 0.025 μg ml−1) of the formation of reactive nitrite radicals, comparable to S2 (52.45 ± 0.825%), and also showed 45.01% site-specific activity (1000 μg ml−1), along with significant (P < 0.05) electron donation potential (50–2000 μg ml−1) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin β-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

Cytotoxic and radioprotective effects of Podophyllum hexandrum.

Podophyllum hexandrum, a herb thriving in Himalayas has already been reported to exhibit antitumor and radioprotective properties. Present study was undertaken to unravel the possible mechanism responsible for the cytotoxic and radioprotective properties of REC-2001, a fraction isolated from the rhizome of P. hexandrum using murine peritoneal macrophages and plasmid DNA as model systems. Cell death, levels of intracellular reactive oxygen species (ROS) and apoptosis were studied employing trypan blue exclusion assay, dichlorofluorescein diacetate and DNA fragmentation assay, respectively. Superoxide anions, hydroxyl radicals and DNA damage were estimated following nitroblue tetrazolium, 2-deoxyribose degradation and plasmid DNA relaxation assays, respectively. Pre-irradiation administration of REC-2001 to peritoneal macrophages in the concentration range of 25-200μg/ml significantly reduced radiation induced ROS generation, DNA damage, apoptosis and cell killing in comparison to radiation control group indicating radioprotective potential. Studies with plasmid DNA indicated the ability of REC-2001 to inhibit 20Gy induced single and double strand breaks further supporting the antioxidative potential. However, REC-2001 in a dose-dependent fashion induced cell death, ROS and DNA fragmentation indicating the cytotoxic nature. REC-2001, in presence of 100μM copper sulfate, generated significant amount of hydroxyl radicals and superoxide anions indicating ability to act as a pro-oxidant in presence of metal ions. The superoxide anion generation was found to be sensitive to metal chelators like EDTA and deferoxamine mesylate (DFR). These results suggest that the ability of REC-2001 to act as a pro-oxidant in presence of metal ions and antioxidant in presence of free radicals might be responsible for cytotoxic and radioprotective properties.

Radiomodulatory and Free-Radical Scavenging Activity of the Fractionated Aquo-Alcoholic Extract of the Adaptogenic Nutraceutical (Rhodiola imbricata)—A Comparative In Vitro Assessment with Ascorbate

Objective: Immense interest has been generated in recent years for the development of drugs of herbal origin for the mitigation of deleterious effects of environmental pollutants like ionizing radiation, mainly to protect against radiation leakages resulting from mishaps in nuclear reactors, deliberate use of dirty bombs, etc. Method: The radio modifying effects of a fractionated extract of the high-altitude Himalayan plant species Rhodiola imbricata, along with its electron-donation potential, super-oxide ion scavenging (IC50 ≤ 0.025 mg/ml), nitric oxide (NO) scavenging potential (IC50 = 0.5 mg/ml), and antihemolytic activity were evaluated in the present study. Reducing power, superoxide ion (O2•−), and nitric oxide scavenging ability of the fractionated extract increased in a dose-dependent manner. Rhodiola imbricata also exhibited antihemolytic potential preventing radiation-induced membrane degeneration of human erythrocytes. Conclusion: Thus, it can be stated that Rhodiola imbricata provides protection against gamma radiation via multifarious mechanisms that act in a synergistic manner. Rhodiola imbricata is widely used as a nutraceutical supplement in the trans-Himalayan region nations, and the current study shows that Rhodiola has immense potential for alleviation of biological damage in a radiation environment.

Urea‐Mediated Regioselective Nitration of (20S)‐Camptothecin

Abstract A facile and efficient procedure for the regioselective nitration of (20S) camptothecin, using urea mediated reagent system under relatively mild experimental conditions, yielding promising anticancer drug 9‐nitro‐ (20S)‐camptothecin in 40% yield with purity of 94.5% (on HPLC) is being reported. #Indian Patent 1559/DEL December 21, 1999.

Aminoalkylation of 10‐Hydroxycamptothecin Using Methylene Chloride Under Solid–Liquid Phase Transfer Catalysis: A New Approach for the Preparation of Topotecan

Abstract The use of dichloromethane as a reagent, for the preparation of Topotecan {(4S)‐10‐(dimethylamino)methyl‐4‐ethyl‐4,9‐dihydroxy‐1‐H‐pyrano[3′,4′:6,7]indolizino‐[1,2‐b]quinoline‐3,14(4H,12H)dione} from 10‐hydroxy‐camptothecin under solid–liquid phase transfer catalysis, which behaves both as a solvent and a reagent serving as for C‐1 unit source for amino‐alkylation of 10‐hydroxy‐(4S)‐camptothecin. #US Patent no. 6,660,861 December 9, 2003.