Prashantha Naik

Synthesis and antitumor activity studies of some new fused 1,2,4-triazole derivatives carrying 2,4-dichloro-5-fluorophenyl moiety

A series of 3-(2,4-dichloro-5-fluorophenyl)-6-(substituted phenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (4) (Fig. 1) have been synthesized by the cyclization of 3-(2,4-dichloro-5-fluorophenyl)-1,2,4-triazol-5-thiol (3) with substituted phenacyl bromides. All the newly synthesized compounds were confirmed by IR, (1)H NMR and mass spectral studies. Among the compounds tested for their antitumor activity three compounds exhibited in vitro antitumor activity with moderate to excellent growth inhibition against a panel of sixty cancer cell lines of leukemia, non-small cell lung cancer, melanoma, ovarian cancer, prostate and breast cancer. The compound 4d showed promising antiproliferative activity with GI(50) values in the range of 1.06-25.4 microM.

Cytogenetic evaluation for genotoxicity of bisphenol-A in bone marrow cells of Swiss albino mice.

Bisphenol-A (BP-A) is a xenobiotic estrogenic compound used in a wide range of consumer products. BP-A was tested for its genotoxicity by employing three cytogenetic assays, viz., chromosomal aberration test, micronucleus assay and test for c-mitotic effects in Swiss albino mice. Studies were carried out for three doses, 10, 50 and 100 mg/kg in single oral exposure and 10 mg/kg in repeated oral exposure (for 5 days). It is evident from the present investigation that although BP-A failed to induce conventional chromosomal aberrations and micronuclei, its genotoxic potential was manifested in the form of achromatic lesion and c-mitotic effects in the bone marrow cells. It can also be speculated from the results that the threshold concentration of BP-A required for the formation of MN is much higher than that for the induction of c-mitotic effects.

Synthesis, characterization of new imidazoquinonyl chalcones and pyrazolines as potential anticancer and antioxidant agents

In the present work, we report the facile synthesis, characterization and anticancer, antioxidant study of new imidazoquinoline carrying biologically active chalcone (2a–d) and pyrazoline (3a–d, 4a–d) moieties. Pyrazoline derivatives (3a–d, 4a–d) have been synthesized from the intermediate chalcones (2a–d) by cyclizing with hydrazine hydrate and phenyl hydrazine. The structures of these compounds were confirmed by IR, 1H NMR, 13C NMR and LC–MS. Biological studies of the synthesized compounds showed promising anticancer and antioxidant activities. The compounds were tested for their in vitro anticancer activity against human cell culture HeLa (cervical cancer) cell line. Compounds 2d and 3d showed the highest cytotoxicity. Compounds 2a, 2d and 3d are found to be the most effective antioxidant agents. Thus, the results show that synthesized compounds possess anticancer and antioxidant activity.

Assessment of genotoxicity of aluminium acetate in bone marrow, male germ cells and fetal liver cells of Swiss albino mice.

Aluminium acetate (AA) has many pharmaceutical applications, which necessitates a thorough evaluation of its toxicity. Dose- and time-dependent genotoxic effects of AA were investigated in Swiss albino mice after exposure via intraperitoneal (i.p.) injection, by employing assays to detect chromosomal aberrations (CA) and micronuclei (MN) in bone marrow, MN in fetal liver, and abnormalities in sperm. Animals were treated with single doses of 50, 100 and 150mg/kg body weight (bw), and with daily doses of 50mg/kg bw for seven consecutive days, in order to study the effects of acute and cumulative doses, respectively. Post-treatment sampling was done at 24, 48 and 72h for bone-marrow CA and MN tests, to study time-dependent effects. Both single and repeated exposures of AA induced chromosomal aberrations, which were dose and time-dependent. The MN test failed to demonstrate genotoxicity after the single-dose exposures, indicating that a higher threshold dose is required for MN induction. Repeated treatment of AA, however, induced MN formation even at the low dose (P<0.05), reflecting genotoxicity following chronic/sub-chronic exposure. A significant reduction in mitotic index and in the P/N (polychromatic/normochromatic erythrocytes) ratio suggests that AA also has a mitodepressive effect in bone-marrow cells. AA-induced germinal genotoxicity was evident from a significant and dose-dependent increase in the percentage of abnormal spermatozoa and a reduction in sperm count. Transplacental exposure of AA resulted in the dose-dependent increase in the frequency of micronucleated erythrocytes in the developing fetus. Thus, the current in vivo study revealed genotoxic effects of AA both on somatic and germ cells of Swiss albino mice.

Microstructural, thermal and antibacterial properties of electron beam irradiated Bombyx mori silk fibroin films

The Bombyx mori silk fibroin (SF) films were prepared by solution casting method and the effects of electron beam on structural, thermal and antibacterial responses of the prepared films were studied. The electron irradiation for different doses was carried out using 8 MeV Microtron facility at Mangalore University. The changes in microstructural parameters and thermal stability of the films were investigated using Wide Angle X-ray Scattering (WAXS) and thermogravimetric analysis (TGA) respectively. Both microstructuralline parameters (crystallite size and lattice strain (g in %)) and thermal stability of the irradiated films have increased with radiation dosage. Agar diffusion method demonstrated the antibacterial activity of SF film which was increased after irradiation on both Gram-positive and Gram-negative species.

Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC50) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.

Structural, surface wettability and antibacterial properties of HPMC-ZnO nanocomposite

The developed hydroxypropyl methylcellulose (HPMC)/Zinc oxide (ZnO) nanocomposite films were examined for structural property and surface wettability using X-ray diffraction and contact angle measurement. Antibacterial activity of these films was evaluated as a function of ZnO concentration. The microstructuralline parameters ( and (g in %)) decreased with increasing concentration of ZnO nanoparticles and there was increase in hydrophilicity. Addition of ZnO nanoparticles in films resulted in antimicrobial activity against tested microorganisms.

Synthesis of novel thiadiazolotriazin-4-ones and study of their mosquito-larvicidal and antibacterial properties.

A series of novel 3-tert-butyl-7-(aryloxymethyl)-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones (5a-5n) were synthesized by refluxing 3,3-dimethyl-2-oxobutanoic acid (trimethyl pyruvic acid) (1) and thiocarbohydrazide (2) in ethanol as solvent for 12 h, to yield 3-mercapto-4-amino-6-tert-butyl-1,2,4-triazine-5(4H)-one (3) (Scheme 1), then the compound (3) was condensed with different substituted aryloxyacetic acids (4) in POCl3 at 90 °C for 8 h (Scheme 2). The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, elemental analyses and mass spectroscopic studies. Few of the synthesized compounds exhibited moderate mosquito-larvicidal and antibacterial activities. Among the novel derivatives, the compound (5f) showed relatively high larvicidal activity against a malaria vector. Compounds (5i) and (5m) exhibited a broad spectrum antibacterial activity against Gram positive and Gram negative species and hence they may be considered as drug candidates for bacterial pathogens.

Genoprotective effects of lignin isolated from oil palm black liquor waste

Black liquor waste (BLW), a major by-product of palm oil extraction process contains lignin as one of the constituents. Lignin isolated from BLW was evaluated for antioxidant and genoprotective properties and was compared with the commercial lignin for overall efficacy. Antioxidant compounds (phenolics and tannins) and antioxidant activities (phosphomolybdenum assay, ABTS(+) and FRAP assays) of lignin isolated from BLW were compared with commercial lignin. Bone marrow micronucleus (MN) test was employed for evaluating the dose-yield protective effect against cyclophosphamide (CP, 50mg/kg b.w.) induced genotoxicity in mouse. Results revealed isolated lignin to exhibit rich antioxidant activities. A decrease in MN frequency and recovery of P/N ratio (P: polychromatic erythrocytes, N: normochromatic erhythocytes) indicated protective effects of lignin against cyclophosphamide induced genotoxicity and cytotoxicity. The efficacy of BLW-derived lignin as an antioxidant and genoprotective agent was comparable to commercial lignin. Results on lignin isolated from BLW are envisaged to find potential applications in food and/or pharmaceutical industries.