C. Ganesh Kumar

Extracellular synthesis of silver nanoparticles using culture supernatant of Pseudomonas aeruginosa.

Bio-directed synthesis of metal nanoparticles is gaining importance due to their biocompatibility, low toxicity and eco-friendly nature. We used culture supernatant of Pseudomonas aeruginosa strain BS-161R for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Pseudomonas aeruginosa culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, EDAX, FT-IR and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 430 nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were mono-dispersed and spherical in shape with an average particle size of 13 nm. The EDAX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FT-IR analysis revealed that the protein component in the form of enzyme nitrate reductase and the rhamnolipids produced by the isolate in the culture supernatant may be responsible for reduction and as a capping material. The XRD spectrum showed the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against gram-positive, gram-negative and different Candida species at concentrations ranging between 4 and 32 μg ml(-1).

Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles.

The recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. Considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of Delftia sp. strain KCM-006 and their application as antifungal agents and as a drug carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical and monodispersed silver nanoparticles with an average size of 9.8 nm. The synthesized nanoparticles were found to be photoluminescent, highly stable and crystalline in nature having a zeta potential of -31 mV. The silver nanoparticles exhibited very good antifungal activity against various pathogenic Candida strains. Furthermore, the efficacy of nanoparticles was increased by conjugating the antifungal drug Miconazole to silver nanoparticles which exhibited significant fungicidal activity, inhibition of ergosterol biosynthesis and biofilm inhibition by increasing ROS levels. In addition, the cell viability and immunocytochemistry analysis against different normal cell lines including Chinese hamster ovary cells (CHO), human lung cell line (MRC5) and human vascular endothelial cells (HUVEC) demonstrated that these nanoparticles were non-toxic up to a concentration of 20 μM. In conclusion, these results suggest that the synthesized nanoparticles find application as both antifungal agents and drug delivery vehicles. This is a first report on the preparation of silver nanoparticles using culture supernatant from Delftia sp. and also on the conjugation of Miconazole, an antifungal drug, to the bacterial silver nanoparticles.

Synthesis of novel 1,2,3-triazole substituted-N-alkyl/aryl nitrone derivatives, their anti-inflammatory and anticancer activity.

A series of novel 1,2,3-triazole substituted N-phenyl nitrone derivatives 5a-e were prepared in three steps starting from 1-substituted-1,2,3-triazole-4-carbaldehydes 2 via Schiffs base formation, reduction followed by oxidation. Similarly, 1,2,3-triazole substituted N-alkyl nitrone derivatives 6a-p were prepared in single step starting from compound 2 on reaction with N-alkyl hydroxylamine hydrochlorides. All the final compounds were screened for anti-inflammatory and anticancer activity against various cancer cell lines. Among the compounds tested, the compounds 5a, 5d, 6a, 6b, 6m and 6o exhibited significant inhibition of IL-1β secretion as a measure of anti-inflammatory activity. Compound 5b, 5c, 6h, 6i and 6o exhibited significant activity against all the cell lines (A549, COLO 205, MDA-MB 231 and PC-3) at IC50 values of <15 μM.

Synthesis, cytotoxicity, antimicrobial and anti-biofilm activities of novel pyrazolo[3,4-b]pyridine and pyrimidine functionalized 1,2,3-triazole derivatives

A series of novel pyrazolo[3,4-b]pyridine and pyrimidine functionalized 1,2,3-triazole derivatives 8a-g and 9a-g were prepared starting from 6-trifluoromethylpyridine-2(1H)one 2 via selective O-alkylation, followed by cyclisation using hydrazine hydrate to obtain 6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 4. Compound 4 was diazotized followed by reaction with sodium azide, resulted in 3-azido-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine 5. Compound 5 was further cyclized with N-/O-propargylated pyrimidine derivatives under Sharpless conditions and obtained compounds 6 and 7, respectively. Each set of compounds 6 and 7 were alkylated with different alkyl halides and obtained respective products 8 and 9. All the products were screened for cytotoxicity against four human cancer cell lines such as A549-Lung (CCL-185), MCF7-Breast (HTB-22), DU145-Prostate (HTB-81) and HeLa-Cervical (CCL-2), compounds 9d, 9e and 9f which showed promising activity have been identified. The products were also screened for antimicrobial, anti bio-film and MBC activities. Promising compounds in each case have been identified.

Synthesis of novel benzo[4,5]thiazolo[1,2-a]pyrimidine-3-carboxylate derivatives and biological evaluation as potential anticancer agents

A novel series of building blocks consisting of benzo[4,5]thiazolo[1,2-a]pyrimidine-3-carboxylate have been synthesized as potential anticancer compounds. These compounds were prepared from 2-aminobenzothiazole, benzaldehyde and ethyl acetoacetate in ethylene glycol by catalysing with TBAHS to give benzo[4,5]thiazo[1,2-a]pyrimidine derivative 4 followed by the formation of amide by reaction with several secondary amines in good yields. The cytotoxicity of these compounds was evaluated against human cancer cell lines in vitro (A549, HeLa, MDA-MB-231 and MCF-7). Compound 5b exhibited promising cytotoxicity with IC₅₀ values of 0.58 and 1.58 μM specifically against human breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, while compound 5a showed promising cytotoxicity against MDA-MB-231 (IC₅₀ value of 5.01 μM).

Physicochemical characterization and antioxidant activity of melanin from a novel strain of Aspergillus bridgeri ICTF-201

Aims:  The aim of the study is to isolate and characterize a melanin pigment from a new strain of Aspergillus bridgeri isolated from rhizosphere soil of Eucalyptus tree and to investigate its antioxidant activity.

Studies on the synthetic and structural aspects of benzosuberones bearing 2, 4-thiazolidenone moiety as potential anti-cancer agents.

Novel representative of the important group of biologically active benzosuberones bearing 2, 4-thiazolidenone moiety was synthesized as potential anticancer agents (6a-j). These compounds were synthesized in good yields from Knoevenagel condensation of compounds 2a-b with thiazolidenone derivatives 3a-e in the presence of sodium acetate and glacial acetic acid. The in vitro cytotoxicity of these compounds was evaluated against different human cancer cell lines (A549, HeLa, MDA-MB-231, MCF-7) and normal cell line, HEK293. Compound 6a exhibited promising cytotoxicity with IC₅₀ values ranging from 2.98 to 13.34 μM against all the tested cancer cell lines, HeLa, A549, MCF-7 and MDA-MB-231, while compound 6g showed potent cytotoxicity against human breast adenocarcinoma cell line (MCF-7, IC₅₀ value of 1.91 μM).

Green synthesis of bacterial gold nanoparticles conjugated to resveratrol as delivery vehicles

Bio-directed synthesis of metal nanoparticles is gaining importance in view of their biocompatibility, low toxicity and eco-friendly characteristics. The present study describes the application of resveratrol conjugated gold nanoparticles as effective delivery vehicles. The green chemistry approach was used for the synthesis of gold nanoparticles by using the culture supernatant of Delftia sp. strain KCM-006. The synthesized gold nanoparticles were mono-dispersed, spherical in shape with an average size of 11.3 nm. They were found to be photoluminescent and crystalline in nature with a zeta potential of -25 mV, indicating their high stability. Resveratrol, an anticancer drug, was conjugated to these gold nanoparticles (RSV-AuNP). The cell viability and immunocytochemistry analysis with human lung cancer cell line (A549) demonstrated that RSV-AuNPs were 65% more effective as drug when compared to resveratrol alone. In vitro observations on the drug release from these nanoparticles exhibited pH dependency; the release was significant (95%) under acidic conditions (pH 5.2) when compared to physiological conditions (pH 7.4).

Anti-tubercular agents. Part 8: synthesis, antibacterial and antitubercular activity of 5-nitrofuran based 1,2,3-triazoles.

A series of 5-nitrofuran-triazole conjugates were synthesized and evaluated for their antimicrobial activity against both Gram-positive and Gram-negative bacterial strains. All the compounds exhibited promising inhibition towards Gram-positive pathogenic strains, while mild inhibitory effects were observed towards Gram-negative bacterial strains. Some of the compounds 8a, 8b, 8e, 8f, 8h are most active among the series exhibiting MIC value of 1.17 μg/ml against different bacterial strains. The bactericidal activity is found to be in accordance with the bacterial growth inhibition data. Compound 8e was found to be equipotent to the standard drug Ciprofloxacin displaying MBC value of 1.17 μg/ml against the bacterial strain Bacillus subtilis. The compounds have also demonstrated promising antibacterial activity against the resistant strain MRSA and were found to be effective inhibitors of biofilm formation. The compound 8b exhibited excellent anti-biofilm activity with IC50 value as low as 0.8 μg/ml. These conjugates were also screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Compound 8e showed promising antitubercular activity with MIC value of 0.25 μg/ml. Most of these compounds are less toxic to normal mammalian cells than the widely used antibacterial drug Ciprofloxacin.

Green synthesis of Kocuran-functionalized silver glyconanoparticles for use as antibiofilm coatings on silicone urethral catheters

Microbial infections due to biofilm formation on medical implants are serious complications arising after surgery which can be prevented by using antimicrobial coatings on biomaterial surfaces. We developed a simple, rapid and green chemistry approach for synthesis of silver glyconanoparticles (AgNPs) using Kocuran, an exopolysaccharide produced by Kocuria rosea strain BS-1. Kocuran-capped AgNPs exhibited a characteristic surface plasmon resonance (SPR) peak around 435 nm. They were mono-dispersed, spherical with an average particle size of 12 nm. XRD and SAED studies suggested that AgNPs were crystalline in nature. AgNPs had a zeta potential of -33.9 mV and were anionic charged. They showed colloidal stability at different pH (6 to 10), temperatures (30 °C to 100 °C), in NaCl, NaNO3 and BSA solutions. Kocuran-capped AgNPs exhibited effective antimicrobial activity against Staphylococcus aureus and Escherichia coli and cell death was mainly due to hydroxyl radical induction and depletion of NADH. They also inhibited the biofilm development by S. aureus and E. coli and confocal scanning laser microscopic images revealed the damage of intact cell architecture. In vitro evaluation of Kocuran-capped silver glyconanoparticles on human gingival fibroblasts demonstrated good cell proliferation as compared to commercial AgNPs suggesting that they are biocompatible and non-toxic in nature. This is a first report on Kocuran-functionalized AgNPs exhibiting potential antibacterial and antiadhesive properties for use as antimicrobial coatings against bacterial adhesion and biofilm formation on silicone urethral catheters.