New2-((2-(2,4-dinitrophenyl)hydrazineeylidene) derivatives: design, synthesis, in silico, and in vitro anticancer studies.

A series of novel hydrazone compounds have been synthesized by the condensation of hydrazines and different substituted salicylaldehydes at a molar ratio of 1:1 in one step reaction and characterized by FT-IR, ESI-MS, 1H NMR, and single crystal x-ray diffraction. The crystal structure of the compound shows a trans configuration around the C = N bond and triclinic system with P -1/-p 1. Synthesized compounds were screened for cytotoxicity activities against A375 (melanoma), HT-29 (Colon), and A549 (lung) cancer cell lines. Among them, compound 2 exhibited the highest cytotoxic effect against the A375 cell line (IC50 = 0.30 µM) and HT-29 cell line (1.68 µM), compared to those of apatinib as a reference standard drug (0.28, 1.49 µM, respectively). The cytocompatibility assay on the L929 normal cell line and the hemolysis assay on human RBC were used to validate the non-toxic action. From DFT calculation, the various parameters such as HOMO-LUMO energies, Hirshfeld, and MEP have been studied. Furthermore, in silico molecular docking with three receptors was studied. Among four compounds, compound 2 has the lowest binding energy against cyclin dependent kinase (ΔGb = -9.3 kcal/mol). In addition to this, molecular dynamics (MD) simulation was also performed. Based on this study, these novel hydrazones can be considered a promising anticancer agent due to their potent cytotoxicity activities and computational analysis.Communicated by Ramaswamy H. Sarma.

Antibacterial potential of ellagic acid and gallic acid against IBD bacterial isolates and cytotoxicity against colorectal cancer.

Ellagic acid and Gallic acid are polyphenols which have shown beneficial effects in animal models of colitis. In the present study Ellagic acid and Gallic acid were evaluated for antibacterial potential against clinical IBD isolates. (HM95, HM233, HM251, HM615). Cytotoxicity was determined against human colorectal adenocarcinoma cells (Caco2, COLO.205, HT.29), whereas, cytocompatibility against normal rat intestinal epithelial (IEC-6) using MTT assay. Ellagic acid showed the lowest MIC and MBC value of 2.5 and 5 mg/mL respectively against HM251 and HM233. Gallic acid exhibited the lowest MIC and MBC value of 1.25 and 2.5 mg/mL respectively against HM251 and HM615. Cytotoxicity assay resulted in reduction of percent cell viability when tested at concentrations ranging from 400-12.5 µg/mL. The polyphenols presented a concentration-dependent deduction in percent cell viability after 48 h exposure It is likely that these polyphenols are good anti-colitic agents. However, further investigations are required.

Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Use of Poly (Ethylene Glycol) Coated Superparamagnetic Iron Oxide Nanoparticles as Radio Sensitizer in Enhancing Colorectal Cancer Radiation Efficacy.

Backgorund: The aim of the radiotherapy is to deliver a lethal dose to tumor while reducing the impact on the normal tissue. This reduction in impact can be achieved to have a greater therapeutic ratio by using nanoparticles as radiosensitizer. Materials and Methods: In this article, the potential role of superparamagnetic iron oxide nanoparticles (SPIONs) as radiosensitization enhancer on HT 29 cell lines for different concentrations (0.007to 0.25 mg/ml) and different radiation doses (0.5to 2 Gy) of 6MV photon beam is presented. Results: The highest sensitization enhancement ratio (SER) value was observed with 2 Gy for 0.25 mg/ml concentration. Radio sensitization increases with increase in the concentration of nanoparticles. Combination of 6MV energy radiation and polyethylene glycol (PEG) coated SPIONs results in increasing cell killing of HT 29 as compared to cell killing with radiation therapy alone. Conclusion: The results reveal that PEG coated nanoparticle might be a potential candidate to work as radiotherapy sensitizer in colorectal cancer.

Isolation, culture and characterization of primary cell lines of human buccal mucosal fibroblasts: A combination of explant enzamytic technique.

BACKGROUND: The cell culture technique has become a routine and a popular method for its wide applications in the field of cell biology and biotechnology and in medical research. Isolation of primary cells over the cancer cells is an essential component of cell culture technology as they are the reliable source to understand normal physiological, morphological and molecular process of human cells. As fibroblasts are the prominent cells of the connective tissue of oral mucosa, many disease entities and histogenesis are linked to fibroblasts. Culture of oral fibroblast cells helps the oral biologists and researchers to study the morphological and molecular process in the oral diseases. AIM: The aim of our experiment is to isolate and culture the human buccal mucosal fibroblast cells from healthy individuals using a combination of explant-enzymatic method and characterization of the cells by short tandem repeat (STR) profiling. MATERIALS AND METHODS: The tissue samples were collected from healthy individuals undergoing routine impacted third molar extraction. A combination of explant-enzymatic technique was used for the isolation from the tissue samples. The cells were further subcultured, maintained and stored as per the standard protocols. Thus, to confirm the oral fibroblasts of human origin and its uniqueness, they were characterized using STR profiling. RESULTS AND CONCLUSION: Using the combination technique, we were successful in isolating the cells at a faster rate by detachment of cells on day 3 and confluency on day 10. The morphological assessment and STR profiling further confirmed that the isolated cell lines resemble human fibroblast cells.

Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation, biocompatibility studies and its antimicrobial activity against periodontal pathogens.

The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.

Designing, validation, and feasibility of integrated yoga therapy module for chronic low back pain.

CONTEXT: Chronic low back pain (CLBP) is a significant public health problem that has reached epidemic proportions. Yoga therapy has emerged as one of the complementary and alternative therapies for CLBP. AIM: The present study reports the development, validation, and feasibility of an integrated yoga therapy module (IYTM) for CLBP. SETTINGS AND DESIGN: This study was carried out at the SVYASA Yoga University, Bengaluru, South India. The IYTM for CLBP was designed, validated, and later tested for feasibility in patients with CLBP. MATERIALS AND METHODS: In the first phase, IYTM for CLBP was designed based on the literature review of classical texts and recently published research studies. In the second phase, designed IYTM (26 yoga practices) was validated by thirty subject matter (yoga) experts. Content validity ratio (CVR) was analyzed using Lawshe's formula. In the third phase, the validated IYTM (20 yoga practices) was tested on 12 patients for pain, disability and perceived stress at baseline and after 1-month of this intervention. RESULTS: A total of 20 yoga practices with CVR ≥0.33 were included, 6 yoga practices with CVR ≥0.33 were excluded from the designed IYTM. The feasibility study with validated IYTM showed significant reduction in numerical pain rating scale (P = 0.02), Oswestry disability scale (P = 0.02), and Perceived Stress Scale (P = 0.03). CONCLUSION: The designed IYTM was validated by thirty yoga experts and later evaluated on a small sample. This study has shown that the validated IYTM is feasible, had no adverse effects and was useful in alleviating pain, disability, and perceived stress in patients with CLBP. However, randomized control trials with larger sample are needed to strengthen the study.