Gallic acid-based indanone derivatives as anticancer agents

Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC₅₀ = 2.2 μM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 μg/ml, 258 μM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.     

Molecular assessment of diversity among endophytic diazotrophs isolated from subtropical Indian sugarcane

Twenty-two endophytic bacterial isolates from the roots of sugarcane were compared morphologically, biochemically and genetically. Gram staining, colony pigment, texture and other cultural characteristics were taken for morphological characterization. Oxidation-fermentation tests for D-glucose and D-sucrose, production of acid and hydrogen from different carbon source, oxidase activity, antibiotic and drug resistance patterns were chosen as the biochemical and physiological criteria. Twelve random decamer primers were used to analyze and compare these isolates through RAPD among themselves as well as with known standard diazotrophic strains. The isolates were compared through dendrograms constructed on the basis of similarity patterns obtained from biochemical and RAPD analysis. The estimated diversity through RAPD analysis was more evident than the diversity on the basis of morphological and biochemical characters. Within Acetobacter group, the isolates showed substantial genetic diversity for future exploitation as PGPRs and diazotrophic associative endophytes.     

Isolation of poly (A)+ mRNA for downstream reactions from some medicinal and aromatic plants

In the present protocol for extraction of RNA, hexadecyltrimethylammoniumbromide (CTAB) and insoluble polyvinylpyrrolidone were used followed by LiCl precipitation, CsCl ultracentrifugation and finally poly (A)+ mRNA was isolated with the help of oligo(dT)-cellulose columns. The isolated poly (A)+ mRNA was found to be suitable for cDNA-AFLP and suppression subtractive hybridization applications. It is a modified and consolidated protocol based on previously described methods for isolated steps and works better for medicinal and aromatic plants. High yield of poly (A)+ mRNA coupled with its amenability for downstream reactions like RT-PCR, northern blotting and cDNA synthesis for library construction is a key feature of the present protocol.     

Plant-based anticancer molecules: a chemical and biological profile of some important leads

A number of natural products, with diverse chemical structures, have been isolated as anticancer agents. Several potential lead molecules such as camptothecin, vincristine, vinblastine, taxol, podophyllotoxin, combretastatins, etc. have been isolated from plants and many of them have been modified to yield better analogues for activity, toxicity or solubility. Several successful molecules like topotecan, irinotecan, taxotere, etoposide, teniposide, etc. also have emerged as drugs upon modification of these natural leads and many more are yet to come. In this review, the authors have focused on four important anticancer leads, that is, camptothecin, taxol, combretastatin A-4 and podophyllotoxin. Their chemistry, structure and activity relationships, biological activities, modes of action, analogue synthesis and future prospects have been discussed.     

Lipid Peroxidation and Antioxidant Activities Involved in Resistance Response against Downy Mildew in Opium Poppy

The aim of this study was to observe the lipid peroxidation (LP) of cell membranes and antioxidant systems in response to inoculation of Peronospora arborescens causing downy mildew (DM) in opium poppy. Contents of the LP product, malondialdehyde (MDA) and antioxidant glutathione (GSH) were determined in leaves of two opium poppy genotypes, Pps‐1 (highly resistant to DM) and Jawahar‐16 (highly susceptible to DM) at different time intervals after inoculation (12 h, 24 h, 48 h and 72 h). The provided GSH content corresponded to that of total non‐protein sulfhydryl groups. In leaves of Jawahar‐16, a significant decrease in concentration of GSH and a persistent increase in concentration of MDA were recorded after inoculation in comparison to leaves of control plants. The continuous decrease in GSH content contributed to damage of cell membranes leading to disease development in Jawahar‐16. On the other hand in a resistant genotype (Pps‐1), initially at 12 h after inoculation (hai) the level of GSH was found to be high, but a transient and highly significant decrease in content of GSH and increase in content of MDA was observed at 24 hai in comparison to control plants of same genotype and also in comparison to inoculated plants of susceptible genotype (Jawahar‐16). These results indicate that generation of GSH and MDA is negatively correlated during the infection process as found in the case of DM‐resistant genotype Pps‐1 at 24hai, which also suggests an increased need by the host plant for oxidative stress, required for hypersensitive response mediated defense mechanism.     

Detection of DNA polymorphism in Papaver somniferum genotypes differing in straw morphinan alkaloid content

Abstract

Thirty‐two distinct accessions of Papaver somniferum were screened for morphinan alkaloid content in the straw. The combined content of major morphinan alkaloids (morphine+codeine+thebaine) was found to vary in the range 0.2260–0.0683%. Two genotypes each, were selected as prototypes for low [I‐48 (0.0683%) and I‐344 (0.0878%)] and high [Pps‐1 (0.2260%) and N‐3 (0.2074%)] morphinan alkaloid content for studying DNA polymorphism. RAPD analysis of these four genotypes using 80 primers could not detect the polymorphism. However, AFLP analysis of these genotypes with 12 EcoRI/MseI primer pairs could distinctly group the high‐ and low‐morphinan alkaloid genotypes separately. Furthermore, 50 AFLP fragments, specific to high‐straw morphinan alkaloid genotypes (Pps‐1 and N‐3) and 28 DNA fragments specific to low‐straw morphinan alkaloid genotypes (I‐48 and I‐344) could be identified. This investigation is the first report on the polymorphism identified in the genotypes differing in their straw morphinan alkaloid content. This DNA polymorphism could be exploited for defining chemotypes at an early seedling stage in poppy breeding programmes.     

Absolute configuration and anticancer activity of taxiresinol and related lignans of Taxus wallichiana

Absolute configuration of taxiresinol 1, a lignan from the heartwood of Taxus wallichiana has been determined as 8R, 8'R, and 7'R with the help of chemical correlation method and X-ray crystallography. The anticancer activity of taxiresinol 1 and other two lignans 2, 3 were also studied. Taxiresinol 1 showed notable anticancer activity in the in vitro bioassays against colon, liver, ovarian and breast cancer cell lines.     

Molecular Profiling for Genetic Variability in <Emphasis Type="Italic">Capsicum</Emphasis> Species Based on ISSR and RAPD Markers

The taxonomic identity of Capsicum species is found to be difficult as it displays variations at morpho-chemical characters. Twenty-two accessions of six Capsicum species, namely, C. annuum, C. baccatum, C. chinense, C. eximium, C. frutescens, and C. luteum were investigated for phenotypic diversity based on flower color and for genetic differences by molecular makers. The genetic cluster analyses of 27 RAPD and eight ISSR primers, respectively, revealed genetic similarities in the ranges of 23–88% and 11–96%. Principal component analysis of the pooled RAPD and ISSR data further supports the genetic similarity and groupings. Different species showed variations in relation to corolla shade of flower. C. annuum accessions formed a single cluster in the molecular analysis as maintaining their flower characteristic. C. chinense accession shared flower features with the accessions of C. frutescens and were found to be closer at genotypic level. C. luteum was found to be rather closer to C. baccatum complex, both phenotypically and genetically. The only accession of C. eximium presenting purple flowers falls apart from the groupings. The floral characteristics and the molecular markers are found to be useful toward the delineation of the species specificity in Capsicum collection and identification of genetic stock.     

Influence of Body Mass Index and Albumin on Perioperative Morbidity and Clinical Outcomes in Resected Pancreatic Adenocarcinoma

Obesity is a known risk factor for PDA and recent reports suggest obesity has a negative impact on clinical outcomes in patients with PDA. Pretreatment body mass index (BMI) and serum albumin (SA) have been shown to be associated with worse overall survival in patients with advanced and metastatic PDA. However, minimal data exists on the impact of BMI and SA on perioperative and long-term clinical outcomes in patients with early-stage resected PDA. Herein, we report on the impact of these variables on perioperative clinical outcomes, overall survival (OS) and disease free survival (DFS) in patients with resected PDA. With IRB approval, we evaluated 1,545 patients with PDA treated at a single institution from 2007–2013 and identified 106 patients who underwent upfront resection with curative intent. BMI and SA were calculated preoperatively and at the time of last clinical evaluation. Influence of preoperative BMI, SA, change in either variable, and influence of other clinical and pathologic variables on perioperative morbidity and mortality was assessed. The impact of these variables on DFS and OS was assessed with cox regression modeling and ANOVA. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Median follow up time was 16 months (3–89). Mean age was 68 years. Median survival was 14 months (3–65) and median time to recurrence was 11 months (1–79). Length of hospital stay was associated with BMI (p = .023), change in BMI (p = .003) and SA (p = .004). Post-operative transfusion rate was associated with SA (p = .021). There was a strong correlation between BMI change and positive margin (p = .04) and lymph node status (p = .01). On multivariate analysis, change in SA (p = .03) and node positivity (p = .008) were associated with decreased DFS. Additionally, preoperative SA (p = .023), node positivity (p = .026) and poor differentiation (p = .045) were associated with worse OS on multivariate analysis. Low preoperative SA was associated with worse DFS and OS in patients with resected PDA. Lower BMI and SA were associated with longer post-operative hospital stay. Our study is one of the first to describe how pre-operative BMI and SA and post-operative changes in these variables impact clinical and perioperative outcomes. This data supports nutritional status and weight loss as predictors of outcome in resected pancreatic cancer patients and warrants further prospective investigation.     

Efficacy of CIM 1166, a combination of compounds derived from Mentha spp. in alleviating experimental vulvovaginal candidiasis in mice

Candida albicans is yeast that is most often associated with serious fungal infections and can cause fungal diseases in immuno-compromised patients especially patients suffering from AIDS, cancer and cases of organ transplant. Amongst women, candidal vaginitis is predominantly caused by strains of Candida albicans and also remains to be a common problem in immuno-competent or healthy women. A study was undertaken to assess the efficacy of a compound CIM 1166 obtained from plant source which was found to possess promising antimicrobial property under in vitro conditions especially against C. albicans. Taking the lead further, a small animal model utilizing aged Swiss albino females that had parturated at least three times were taken up for model development. Infection (7 × 10⁶ cfu/ml) was instilled into the vagina in a volume of 20 μl for 3 days. Vaginal washings were aseptically collected on day 4th to confirm the establishment of infection following which the treatment was started which continued for the next 5 days through vaginal route. Vaginal washings were collected on 6th day and the colony forming units were enumerated on chloramphenicol incorporated SDA plates. The results indicated that there was a significant decrease in the colony forming units in vaginal washings (8.0 × 10² cfu/ml) of the treated animals as compared to blank control group (6.0 × 10⁴ cfu/ml). The positive control group administered with clotrimazole also showed a recovery from infection with a fungal load of 8.78 × 10² cfu/ml. The study proves the efficacy of CIM 1166 in curing vaginal candidiasis in mice, which can be taken up for formulation development and further studies.