Y. Poornachandra

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.

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.

Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-Chromene derivatives and their cytotoxic activity.

A series of novel 2-(1,2,3-triazolylmethoxy) 5a-q and isoxazole tagged 6a-g 2H-Chromene derivatives were prepared starting from salicylaldehyde and ethyl-4,4,4-trifluoroacetoacetate via cyclization to form ethyl 2-hydroxy-2-(trifluoromethyl)-2H-Chromene-3-carboxylate 3. Compound 3 on reaction with propargyl bromide resulted compound 4 and was independently reacted with aryl/alkyl azides and aryl aldoximes obtained 2-(1,2,3-triazolylmethoxy) and isoxazole tagged 2H-Chromene derivatives 5a-q, 6a-i, respectively. Compounds 6 were further hydrolysed to acid derivatives 7a-g. All the products 5a-q, 6a-i, 7a-g were screened for cytotoxic activity against four human cancer cell lines and among all the compounds, 5f, 5g, 5l, 5q showed promising activity at <20 μM concentration.

Synthesis of novel benzimidazole functionalized chiral thioureas and evaluation of their antibacterial and anticancer activities.

A small library of benzimidazole functionalized chiral thioureas was prepared starting from natural amino acids (S)-alanine, (S)-phenylalanine, (S)-valine and (S)-leucine and also their (R)-isomers and studied their antimicrobial activity against a various Gram-positive and Gram-negative bacterial strains. In this study, compounds 5g and 5j were found to exhibit good antibacterial activity against both Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Klebsiella planticola, Escherichia coli and Pseudomonas aeruginosa. In the cytotoxicity study, thioureas derived from non-natural amino acids 5a-l showed good activity against human cancer cell lines A549, MCF7, DU145, HeLa, and no cytotoxicity was observed with their antipodes 6a-l.

Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents

A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule.

One-pot catalyst free synthesis of novel kojic acid tagged 2-aryl/alkyl substituted-4H-chromenes and evaluation of their antimicrobial and anti-biofilm activities.

A number of 3-hydroxy-6-(hydroxymethyl)-2-(2-phenyl-4H-chromen-4-yl)-4H-pyran-4-ones (3) have been synthesized in a one pot catalyst free reaction of 2-hydroxy chalcone (1) with kojic acid (2) in toluene at reflux temperature and evaluated for antimicrobial and anti-biofilm activities. Compounds 3a, 3e, 3f, 3l showed potent antimicrobial activity against Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, whereas 3b and 3k exhibited excellent activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, while 3g showed promising activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739. On the other hand, compounds 3a, 3b and 3l showed very good anti-biofilm activity and 3g showed moderate activity against Bacillus subtilis MTCC 121. Whereas, compounds 3a and 3f showed moderate activity against Escherichia coli MTCC 739, while compounds 3a, 3b, 3k and 3l displayed similar activity against Staphylococcus aureus MLS-16 MTCC 2940.

Synthesis, antimicrobial and anti-biofilm activities of novel Schiff base analogues derived from methyl-12-aminooctadec-9-enoate.

A novel library of Schiff base analogues (5a-q) were synthesized by the condensation of methyl-12-aminooctadec-9-enoate and different substituted aromatic aldehydes. The synthesized compounds were thoroughly characterized by spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, ESI-MS and HRMS). The Schiff base analogues with different substitutions were screened for in vitro antibacterial activity against 7 different bacterial strains. Among these, the compounds with electron withdrawing substituent, namely chlorine (5a) and electron donating substituents, namely hydroxy (5 n) and methoxy (5 o), were found to exhibit excellent to good antimicrobial activities (MIC value 9-18 μM) against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS-16 MTCC 2940 and Bacillus subtilis MTCC 121. The products were also screened for anti-biofilm and MBC (Minimum Bactericidal Concentration) activities which exhibited promising activities.