Bhupendra Mistry

Time and Concentration-Dependent Therapeutic Potential of Silver Nanoparticles in Cervical Carcinoma Cells.

Silver nanoparticles (AgNPs) have well-known anti-bacterial properties and have been widely used in daily life as various medical and general products. There is limited information available on the cytotoxicity of AgNPs. Therefore, the present study aimed to investigate the cytotoxicity of AgNPs in HeLa cells. Cytotoxicity and apoptosis have been observed in the AgNPs treated in the HeLa cells. Sulphorhodamine-B assay (SRB assay) showed the cytotoxic effect in the AgNP-treated HeLa cells. Inverted microscope, fluorescence microscope, and confocal laser scanning microscope (CLSM) analyses showed the apoptosis-induced morphological changes such as rounding in shape, nuclear fragmentation, cytoplasm reduction, loss of adhesion, and reduced cell volume. Necrosis and apoptosis were observed in the AgNP-treated HeLa cells by DNA fragmentation study. Mitochondria-derived reactive oxygen species (ROS) have increased in AgNP-treated HeLa cells. Up-regulation of messenger RNA (mRNA) expression of p53, bax, and caspase 3 were found in AgNP-treated HeLa cells. Caspase 3 enzyme activity was found to increase in AgNP-treated HeLa cells. The AgNPs showed the right cytotoxic effect in cervical carcinoma cells. Our results suggest that metal-based nanoparticles might be a potential candidate for the treatment of cervical cancer.

Chrysin-benzothiazole conjugates as antioxidant and anticancer agents.

7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

Investigation of role of aspartame on apoptosis process in HeLa cells

Aspartame is an artificial sweetener used as an alternate for sugar in several foods and beverages. The study reports that consumption of aspartame containing product could lead to cancer. However, the effect of aspartame on apoptosis process in cancer is not yet understood clearly. HeLa cells were exposed to different concentrations (0.01–0.05 mg/ml) of aspartame for 48 h. Cytotoxicity of aspartame on cancer cells was determined by SRB assay. The result indicates no significant changes on cell viability. Aspartame suppresses apoptosis process in cancer cells by down-regulation of mRNA expression of tumor suppressor gene p53, and pro-apoptotic gene bax. It up-regulates anti-apoptotic gene bcl-2 mRNA expression. In addition, Ki 67 and PCNA mRNA, and protein expressions were determined. Taking all these together, we conclude that aspartame may be a potent substance to slow-down the apoptosis process in HeLa cells. Further works are ongoing to understand the biochemical and molecular mechanism of aspartame in cancer cells.

Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects

A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe+3 reducing power in ABTS assay. The radical scavenging potential of the final derivatives 4a–j was found excellent with IC50s, <13 μg/mL and < 8 μg/mL in DPPH and ABTS assay, respectively, whereas some analogues showed significant Fe+3 reducing power with absorption at around 2 nm in the FRAP assay. Anticancer effects of titled compounds were inspected against cervical cancer cell line Hela and Caski adapting SRB assay, in which analogues 4a–j presented <6 μg/mL of IC50s, and >30 of therapeutic indices, thus exerting low cytotoxic values against Malin–Darby canine kidney (MDCK) cell lines at CC50s >125 μg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and 1H NMR as well as elemental analyses.

Efficacy of carnosine on activation of caspase 3 and human renal carcinoma cell inhibition

Carnosine is a natural antioxidant dipeptide that is highly concentrated in muscles and brain. The present study investigated the effect of carnosine cell growth inhibition and activation of the caspase-3 enzyme under cell co-culture system. Renal carcinoma and normal cells were co-cultured to provide three-dimensional views for the experimental analyses. Carnosine inhibited renal cancer cell growth up to 40%, whereas it was 25% in normal cells. Caspase-3 enzyme activity corresponded to the appearance of immunofluorescence in the cytoplasm using the caspase-3 antibody. Caspase-3 enzyme activity gradually increased in renal carcinoma cells in a concentration-dependent manner. The increased immunofluorescence and fluorescent detection of caspase-3 indicated the occurrence of apoptosis. The binding affinity of carnosine with caspase-3 subunit was confirmed by In silico docking study and glide energy was -5.2kcal/mol. Taking all these data together, it is suggested that the carnosine may be a potential antiproliferative agent in renal carcinoma tumor.

Discovery of berberine based derivatives as anti-influenza agent through blocking of neuraminidase

In this study, we investigated the antiviral activity of newly synthesized berberine derivatives (BD) against influenza virus infection using several strains in in vitro and in silico. The CPE reduction, pre-incubation, NA activity inhibition and molecular docking assays were used for antiviral evaluation. The anti-influenza activities of BDs were stronger than plant-derived pure commercial berberine, and some of the BDs were more potent than control drug Oseltamivir. The cytotoxicity level was observed in the range 63.16-1639μg/mL for synthesized BDs. Additionally, BDs were detected as able to block influenza viral particles. We targeted neuraminidase one of the influenza surface protein for further probing. Moreover, BDs registered competitive NA inhibition activity comparing with Oseltamivir. The active site of viral NA subunit was fully blocked by BD as the same location as Oseltamivir. The binding energies between influenza NA subunit and BD-5 were higher than Oseltamivir. More H-bonds and NA residues were occupied by BD for stronger binding ability than Oseltamivir. These results indicated that BD inhibits various strains of influenza virus by blocking of viral NA subunit.

Chrysin-piperazine conjugates as antioxidant and anticancer agents.

Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.

Paper Waste Extracted α-Cellulose Fibers Super-magnetized and Chitosan-Functionalized for Covalent Laccase Immobilization

Enormous disposal of paper wastes (PW) causing number of environmental problems. PW is efficiently used to extract multifunctional α-cellulose fibers (αCFs). Thus, αCFs extraction from PW, and functionalization with Fe3O4 and chitosan were successfully performed for immobilization of laccase. Therefore, in this investigation, PW extracted αCFs were tuned with supermagnetic Fe3O4 (M) and functionalized with chitosan (CTA) (M-PW-αCF-CTA). Furthermore, M-PW-αCF-CTA was glutaraldehyde cross-linked for covalent laccase immobilization. The synthesized materials were characterized by FT-IR, TGA, FE-SEM, FE-HR-TEM and VSM analyzes. M-PW-αCF-CTA exhibited magnetic saturation value of 14.72 emu/g. Laccase immobilized on M-PW-αCF-CTA (M-PW-αCF-CTA-Lac) gave 92% of activity recovery and loading capacity of 73.30 mg/g. M-PW-αCF-CTA-Lac showed excellent pH, temperature, and storage stabilities with the exceptional reusability potential. Moreover, M-PW-αCF-CTA-Lac was applied for repeated removal of carcinogenic Direct Red 28 (DR28). Therefore, M-PW-αCF-CTA-Lac is green and economical biocatalyst with extraordinary separation potential can be enforced for environmental pollutants reclamation.

Synthesis of Mannich base derivatives of berberine and evaluation of their anticancer and antioxidant effects

The 9-demethylated derivative of the isoquinoline alkaloid berberine was derivatised in its isoquinoline moiety using enamines derived from formaldehyde and morpholine, piperidine, carbazole and six variously substituted piperazines to form Mannich base products which were evaluated for their in vitro biological effects. Standard tests determined their radical scavenging potential and their ferric reducing antioxidant power (FRAP). Cancerous growth inhibitory efficacies were assessed using cervical cancer cell lines HeLa and CaSki and their cytotoxicities towards normal cell lines were evaluated using Madin–Darby canine kidney (MDCK) cell lines. Piperazine derivatives bearing a heterocyclic nitrogen substituent such as a pyridyl or a pyrimidyl ring were the most active antioxidant and anticancer agents. A carbazole moiety attached to the berberine core also demonstrated excellent inhibitory effects on cancerous cells.

Quercetin: A plant-derived polyphenol with tremendous cardioprotective effects

Flavonoids are allocated among various vegetations and in foodstuffs; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans loaded with flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to have potential action towards hypertension, inflammation, diabetes and vascular disease. Their results on LDL lowering, platelet aggregation and vasodilatation recommend an ability to expel the pathophysiology of atherosclerotic plaque formation. Searching for experimental evidence to validate the cardio protective effects of quercetin, we review here the detailed in vivo facts performed in recent years. Quercetin and its derivatives led to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence-based studies suggest mechanisms to observe cardiovascular diseases such as aging effects, hypertension, angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models involving human are used to elucidate the role of quercetin in cardiovascular diseases in vivo. The role of quercetin and its derivatives may go beyond their existence in food and has potential a lead molecule in drug development programs.