Antioxidant activity of erlotinib and gefitinib: theoretical and experimental insights.

Erlotinib and gefitinib are quinazoline derivatives with antineoplastic properties. Usually, intake of antineoplastic agents results in much a greater degree of oxidative stress, i.e. the production of free radicals, than induced by cancer itself. Hence, anticancerous drugs must also exhibit antioxidant activity but this has not been studied thus far. In this study, the antioxidant activity of erlotinib and gefitinib was examined by experimental and computational studies. It was found that erlotinib and gefitinib exhibit good 2,2-dipheny l-1-picrylhydrazyl (DPPH) radical and hydroxyl radical scavenging (HRS) activities. In DPPH assay, the IC50 for erlotinib and gefitinib were 0.584 and 0.696 mM, respectively, while IC50 for HRS assay were 0.843 and 1.03 mM for erlotinib and gefitinib, respectively. Structural characteristics such as frontier molecular orbitals (FMOs), molecular electrostatic potential maps (MESPs), and global descriptive parameters were calculated at DFT/B3LYP/6-311++G (d,p) on the optimized geometries of erlotinib and gefitinib. UV-visible spectroscopy revealed the possible electronic transitions between the FMOs and their associated excitation energies of both drugs and found that erlotinib has π to π* transitions while gefitinib has π to π* and σ to π* transitions. To elucidate the antioxidant activity of erlotinib and gefitinib, three mechanisms namely hydrogen atom transfer (HAT), single electron transfer proton transfer (SETPT), and sequential proton-loss electron-transfer (SPLET) were employed and articulated the results in arithmetic parameters like bond dissociation energy (BDE), proton affinity (PA), ionization potential (IP), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE). Further, molecular docking studies have been carried out to have a better understanding of binding sites and modes of interaction with a well-known antioxidant target protein monoamine oxidase-B (MAO-B) employing docking scores and types of interactions. All the calculated parameters point out that though gefitinib and erlotinib were interchangeable, erlotinib requires a lesser amount of energy for proton transfer and electron transfer, moreover it scavenges radicals easily.

Theoretical insights into the radical scavenging activity of glipizide: DFT and molecular docking studies.

Glipizide is an N-sulfonylurea compound used in the treatment of hyperglycemia in patients with type 2 diabetes mellitus. In the present study, DFT-based computational methods and molecular docking studies have been performed to systematically evaluate the radical scavenger behavior of the title molecule. Structural characteristics such as molecular descriptors, frontier molecular orbitals, molecular potential mapping, and Mulliken charge population have been investigated. Thermodynamic parameters like proton affinity (PA), ionization potential (IP), bond dissociation energy (BDE), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE) related to three antiradical mechanisms namely hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT) and sequential proton loss electron transfer (SPLET) have been studied. Also, molecular docking studies have been carried out to have a theoretical understanding of the molecular mechanism and for the elucidation of binding mode/modes of a compound targeted through non-covalent interactions. The obtained results are of great significance in better understanding the reaction mechanism of the title molecule and opens a new perspective for the design of potent antioxidant agents.

Amelioration of sodium fluoride induced oxidative stress by Cynometra travancorica Bedd in mice.

OBJECTIVES: Cynometra travancorica, endemic to Western Ghats of India is pharmacologically similar to Saraca asoca and occasionally used as substitute in a well-known Ayurvedic uterine tonic Asokarishta. S. asoca possess various biological properties, but there are no reports on C. travancorica. The present study evaluated the pharmacological properties of C. travancorica and its efficacy in attenuating the sodium fluoride (NaF) induced oxidative stress in mice. METHODS: Antioxidant potential of methanolic extract of C. travancorica (CTE) stem bark was evaluated using DPPH, superoxide radical scavenging and total antioxidant assays. The effect of CTE on mitigating NaF deteriorated redox status in the liver tissue of mice was evaluated. Functional groups in CTE were analyzed by FTIR analysis. RESULTS: CTE effectively scavenged the free radicals in in vitro condition. CTE could augment catalase (46.6%), superoxide dismutase (53.8%) activities and GSH level (48.1%) against NaF induced decline in the liver tissue of mice. The peroxidation of lipids was found to be decreased by 44.9% and tissue damage abated as inferred by histopathology. FTIR analysis revealed the presence of biologically active functional groups in CTE. CONCLUSIONS: The study revealed the ameliorative effect of C. travancorica against NaF induced deleterious effect in experimental animals by its potent antioxidant potential.

Neera, a non-fermented traditional drink from coconut spadix restores the redox status in sodium fluoride intoxicated mice.

OBJECTIVES: Neera, non-fermented coconut inflorescence sap (NFCIS) and its fermented form, toddy (FCIS) are the two well-known traditional drinks in South India. Both the saps show high rejuvenation effect and NFCIS is used for the curing of bronchial suffocation, anemia, tuberculosis and piles in traditional medicine. But, a few scientific studies have been reported on their health benefits so far. Presently, the antioxidant effect of both non-fermented (NFCIS) and fermented form (FCIS) of coconut inflorescence were analyzed in experimental animals. METHODS: The free radical scavenging property of FCIS and NFCIS was analyzed in vitro. The effect of these saps on mitigating sodium fluoride (NaF) deteriorated redox status was evaluated in mice. RESULTS: NFCIS exhibited high antioxidant activity than its fermented form. NFCIS reduces metal ions and scavenge hydroxyl and DPPH radicals with IC50 values 6.5 ± 1.9 and 44 ± 3.14 µL/mL, respectively. Supplementation of NFCIS for 14 days increased SOD, CAT and GPx activities and GSH level in liver by 51.67, 52, 27.88 and 35.77%, respectively against NaF induced decline with a concomitant decrease in lipid peroxidation to 40.76%. Saps rich in minerals indicate pharmaceutical and nutritional value. CONCLUSION: The study revealed the antioxidant efficacy of non-alcoholic natural drink, Neera and recommends an alternative for synthetic carbonated soft drinks. The regular consumption of Neera may protect the body from various chronic diseases especially where the oxidative stress played as a key role.

Ameliorative effect of Neera, nonfermented coconut inflorescence sap, on cisplatin-induced renal toxicity by abating oxidative stress.

Objectives Neera, nonfermented coconut inflorescence sap (NFCIS) from unopened spadix of Cocos nucifera L., is a well-known traditional beverage. But, scientific reports on its health benefits are limited. NFCIS is reported to exhibits free radical scavenging activity, and its chemical composition is found promising. In the present study, the effect of NFCIS on alleviating cisplatin-induced nephrotoxicity was analyzed in mice. Methods The renal toxicity was induced by cisplatin (16 mg/kg b.wt. ip) in Swiss albino mice. The antioxidant activity of NFCIS was evaluated by nitric oxide radical scavenging assay and phorbol-12-myristate-13-acetate-induced superoxide radical generation in mice peritoneal macrophages. Total polyphenolic content of sap was determined using Folin-Ciocalteu reagent. The phytochemicals present in NFCIS was identified using Fourier transform infrared (FT-IR) spectroscopy. Results NFCIS was found to scavenge nitric oxide (NO) radicals (IC50 = 32 ± 2.47 µL/mL) and shown to inhibit superoxide (SO) generation (53.5 ± 2.1%) in macrophages. High polyphenolic content (193 µg gallic acid/mL) was determined in the sap. The FT-IR spectrum of NFCIS revealed the presence of several phytochemicals indicate its pharmaceutical and nutritional value. Cisplatin-induced hike in urea, creatinine and lipid peroxidation was significantly decreased to 65.16, 87.74 and 53.41% by NFCIS, respectively. Hb (42.37%) and total count (72.81%) were also found to be increased. Additionally, the activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione was enhanced to 53.06, 40, 52.22 and 38.49%, respectively. Conclusions Results indicate that NFCIS effectively alleviates cisplatin-mediated renal toxicity by its antioxidant activity.

Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential.

Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 µg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 µg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential.