Pombala Sujitha

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.

Iron-catalyzed aryl-aryl cross coupling route for the synthesis of 1-(2-amino)-phenyl)dibenzo[b,d]furan-2-ol derivatives and their biological evaluation

Naturally occurring dibenzofuran motifs represent promising lead structures for the development of novel antimycobacterial agents. Prompted by our recent development of cross dehydrogenative coupling using iron catalysis, we extended our strategy to synthesize 14 novel anilinodibenzofuranols and they were explored for anti-tubercular and cytotoxic activities. Consistent with our hypothesis, DBF-3, 14 and 16 exhibited promising activity against two strains (M. tuberculosis H37Rv and the clinical S, H, R, and E resistant isolate), while DBF-13, 18 exhibited selective inhibitory activity only against the clinical S, H, R and E resistant isolate. However, the compounds DBF-4 and DBF-8 showed promising and selective antitumor activity against the tested cancer cell lines.

Evaluation of critical nutritional parameters and their significance in the production of rhamnolipid biosurfactants from Pseudomonas aeruginosa BS-161R

Eleven biosurfactant producing bacteria were isolated from different petroleum‐contaminated soil and sludge samples. Among these 11 isolates, two were identified as promising, as they reduced the surface tension of culture medium to values below 27 mN m−1. Besides biosurfactant production property, they exhibited good flocculating activity. Microbacterium sp. was identified as a new addition to the list of biosurfactant and bioflocculant‐producers. Optimization of various conditions for rhamnolipid production was carried out for one of the promising isolate, Pseudomonas aeruginosa BS‐161R. Bioglycerol (2.5%), as a cheap renewable carbon source, attained better rhamnolipid yield, while sodium nitrate appeared to be the preferable nitrogen source. The optimum carbon to nitrogen (C/N) and carbon to iron (C/Fe) ratios achieved were 15 and 28,350, respectively, which favored rhamnolipid production. Physical parameters like pH, temperature, and agitation speed also affected the production of rhamnolipids. Results from shake flask optimization indicated that the concentration of bioglycerol, sodium nitrate, and iron were the most significant factors affecting rhamnolipid production, which was supported by the results of central composite rotatable design. After optimization of the culture conditions, the production of rhamnolipids increased by ninefold from 0.369 to 3.312 g L−1.

Hsp90-targeted miRNA-liposomal formulation for systemic antitumor effect

Chaperone protein Hsp90 maintains functional integrity and maturation of a large number of cellular proteins including transcription factors, kinases, etc. It is often over-expressed in cancer cells for simultaneous maintenance of many non-regulated and/or genetically mutated proteins. Small molecule-based regimens inhibiting over-expressing Hsp90 in cancer cells often plagued with improper targeting leading to non-specific toxicity. Recently using a glucocorticoid receptor (GR)-targeted cationic lipoplex, we observed cancer cell-specific GR-transactivation and transgene expression by utilizing an unprecedentedly compromised chaperone-activity of cancer cell-associated Hsp90. In normal cells, GR is expressed ubiquitously and is highly regulated and chaperoned by Hsp90. This does not allow cancer cell-alike GR-mediated transgene expression. As a novel anticancer strategy, we showed that compromising Hsp90 in cancer cells can be utilized to selectively deplete its own level by delivering a specially designed artificial miRNA-plasmid against Hsp90 (amiR-Hsp90). Practically, GR-mediated delivery of amiR-Hsp90 plasmid in tumor-bearing mice, depleted Hsp90, critically down-regulated levels of Akt, VEGFR2 and other Hsp90-client proteins but up-regulated wild-type p53 in tumor. These enforced apoptosis in angiogenic vessels and in tumor mass and significantly shrunk tumor-volume. The present study describes gene therapy strategy against Hsp90 using a new GR-targeted liposome-amiR-Hsp90 lipoplex formulation for treating cancer.

Synthesis, characterization and cytotoxic activity of palladium (II) carbohydrate complexes

AbstractCarbohydrate containing pyridyl triazole ligands, 5-deoxy-1,2-O-isopropylidene-5-(4-(2-pyridyl)-1H-1,2,3-triazole-1-yl)-α-D-xylofuranose (2a), 3-O-Benzyl-5-deoxy-1,2-O-isopropylidene-5-(4-(2-pyridyl)-1H-1,2,3-triazol-1-yl)-α-D-xylofuranose (2b), methyl-5-deoxy-2,3-O-isopropylidene-5-(4-(2-pyridyl)-1H-1,2,3-triazol-1-yl)-β-D-ribofuranoside, (2c) and 6-deoxy-1,2:3,4-di-O-isopropylidene-6-(4-(2-pyridyl)-1H-1,2,3-triazol-1-yl)-α-D-galactopyranose (2d) were prepared by the ‘click’ reaction of 2-ethynyl pyridine with the corresponding azides. The palladium complexes were synthesised by the reaction of pyridyl triazole ligands with [Pd(COD)Cl2] in dichloromethane. All the compounds were characterised by NMR, IR, mass and elemental analysis. Structural characterization of the ligand 2a was done by X-ray crystallography. The ligands and complexes were tested for their cytotoxic activity on different cell lines like A549 (human alveolar adenocarcinoma cells), Neuro2a (mouse neuroblastoma cells), HeLa (cervical carcinoma cancer cells), MDA-MB-231 (human breast adenocarcinoma cells) and MCF7 (human breast adenocarcinoma cells). The complexes showed considerable cytotoxicity while the ligands were non-toxic on the tested cell lines. Graphical AbstractPyridyl-carbohydrate triazole ligands were prepared by means of Cu(II) catalysed 1,3-dipolar cycloaddition reaction. Palladium (II) complexes were prepared by treating these ligands with [Pd(COD)Cl2]. The ligands and their palladium complexes were studied for their cytotoxic activity.

Kocuran, an exopolysaccharide isolated from Kocuria rosea strain BS-1 and evaluation of its in vitro immunosuppression activities.

In an ongoing survey for bioactive potential of microorganisms from different biosphere zones of India, a promising Kocuria rosea strain BS-1 was identified which produced an exopolysaccharide (designated as Kocuran) exhibiting in vitro antioxidant and immunosuppression properties. Kocuran was characterized as a heteropolysaccharide with repeating monosaccharide residues of glucose, galactose, mannose and glucuronic acid with an average molecular mass of 51.2 kDa. In RAW 264.7 macrophages, Kocuran significantly downregulated the LPS-stimulated ROS, NO, TNF-α, IL-6 and C3 complement component secretion to 4.71±0.08%, 4.11±0.06%, 11.19±0.06 pg ml⁻¹, 9.12±0.07 pg ml⁻¹ and 20.81±0.06 ng/10⁶ cells ml⁻¹, respectively. Furthermore, it inhibited the PHA-stimulated proliferation of human peripheral blood mononuclear cells with IC₅₀ of 100.13±2.1 μg ml⁻¹. In addition, the classical and alternative pathway mediated hemolysis was also inhibited with CH₅₀ and AH₅₀ of 100.96±1.75 and 98.60±1.93 μg ml⁻¹, respectively. Kocuran did not inhibit the LPS-induced LAL enzyme and the binding of FITC-LPS to macrophages suggesting that Kocuran does not neutralize the LPS activity. These results demonstrate the in vitro suppression of activation and macrophage-derived inflammatory cytokines and complement mediated hemolysis indicating its in vitro immunosuppression activity.

New bioactive macrocyclic diterpenoids from Jatropha multifida.

Two new macrocyclic diterpenoids, multifidanol (1) and multifidenol (2) along with several known compounds have been isolated from the stem of Jatropha multifida. The structures of the new compounds were established from the extensive studies of their 1D and 2D NMR spectra. The cytotoxic and antimicrobial activities of these two constituents were examined.

Synthesis of novel chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives via domino aldol-type/hetero Diels–Alder reaction and their cytotoxicity evaluation

New chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives have been synthesized by domino aldol-type reaction/hetero Diels-Alder reaction generated from o-quinone methide in situ from 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones with resorcinols/naphthols in the presence of 20 mol% ethylenediamine diacetate (EDDA), triethylamine (2 mL) as co-catalyst in CH3CN under reflux conditions in good yields. The structures were established based on spectroscopic data, and further confirmed by X-ray diffraction analysis. The results showed that compounds 4h and 4j exhibited very potent cytotoxicity against human cervical cancer cell line (HeLa). Compound 4h displayed good inhibitory activity against both breast cancer cell lines, MDA-MB-231 and MCF-7. Further, the compound 4i exhibited good cytotoxicity against only MDA-MB-231, and compound 4j showed promising activity against human lung cancer cell line, A549 with IC50 value of 2.53±0.07 μM, which was comparable to the standard doxorubicin (IC50=1.21±0.1 μM).

Total synthesis of desacetylumuravumbolide, umuravumbolide and their biological evaluation

Stereoselective synthesis of naturally occurring α,β-unsaturated lactones desacetylumuravumbolide and umuravumbolide is described. Commercially available propargyl alcohol was used as the starting material. The key steps of this synthesis were alkynylation, a Noyori asymmetric reduction and Still–Gennari olefination. Additionally, the biological activity of umuravumbolides was evaluated on HeLa, MDA-MB-231, MCF7 and A549 cancer cell lines. Umuravumbolide (2) showed potent anticancer activity.

A new strategy for the synthesis of crucigasterin A, and cytotoxic activity of this compound and its related analogues ☆

Stereoselective total synthesis of bioactive marine natural product crucigasterin A has been accomplished from commercially available and inexpensive L-(-)-malic acid as a starting material. Julia olefination and chelation controlled Grignard additions are the key steps involved in the present synthesis. Cytotoxic properties of crucigasterin A and its related analogues crucigasterins B and D have been evaluated. Crucigasterin A showed promising activities against both the human cervical cancer cell line and human breast adenocarcinoma cell line.