Design and fabrication of functionalized curdlan-curcumin delivery system to facilitate the therapeutic effects of curcumin on breast cancer.

We developed a facile method for the fabrication of a biodegradable delivery system composed of two blocks: curdlan and curcumin. This was achieved by chemical functionalization of curdlan through tosylation, amination followed by complexation with curcumin. A comprehensive evaluation of structural characterization and component stability showed that cur-cum complex exhibited better anticancer properties with enhanced thermal properties. The cur-cum complex shows pH sensitive sustained release behaviour with higher release at acidic pH and kinetic data of drug release follows the Korsmeyer-Peppas model. The cur-cum complex has ability to block the proliferation of the MCF-7 cell line as revealed by MTT assay which showed increased toxicity of cur-cum complex against these cell lines. The results obtained from western blot analysis demonstrated that the co-administration of cur and cum effectively induced apoptosis in MCF-7 cells. This effect was observed by a considerable upregulation of the Bcl-2/Bax ratio, a decline in mRNA expression of LDHA, level of lactate and LDH activity. The results clearly depict the role of functionalized curdlan as efficient carrier for curcumin delivery with prolonged, sustained release and enhanced bioavailability, thereby improving the overall anticancer activity.

Fabrication of metal incorporated polymer composite: An excellent antibacterial agent.

US Food and Drug Administration (FDA) allowed for direct addition of castor oil for human consumption as food and most recently FDA approved castor oil as over-the-counter (OTC) for laxative drug. The present article highlights the green route phosphorylation of castor oil (COL) via condensation polymerization. Further, the incorporation of metal ions Cu (II)) and Zn (II) into the polymer matrix have been carried out at elevated temperature using catalyst p-toluene sulphonic acid (PTSA). The modification of the said material has been confirmed by FT-IR, UV-VIS, and 1H and 31P-NMR spectroscopy. Further, the in vitro antibacterial activities of the metal incorporated-COL has been performed by standard methods against B. cereus (MCC2243) (gram-positive) and E. coli (MCC2412) (gram-negative) bacteria. The results revealed that the incorporation of metal ions into the polymer matrix increases the antibacterial activity largely. This may be governed by the electrostatic interaction between metal ions and microbes, also the generation of free active oxygen hinders the normal activity of bacteria. These results suggest that the synthesized material may act a potential candidate for low cost, environment friendly antibacterial agents and may find their application in clinical fields. Herein we are also proposing mechanism of antibacterial activity.

S-benzyldithiocarbazate imine coordinated metal complexes kill Candida albicans by causing cellular apoptosis and necrosis.

Development of new chemotherapeutic agents and strategies are urgently needed to curb and halt the growing menace caused by hard-to-treat microbes. Coordination of metals to bioactive organic ligands is now considered to be an efficient strategy for delivering bioactive compounds inside the microbial cell membranes. Metal complexes have been effectively used to treat many dreadful diseases were other treatment modalities had failed. Use of metal complexes to treat microbial infections is now conceived to be an alternative and efficient strategy. Towards this, some new homoleptic transition metal complexes, obtained by coordination of metal ions to bioactive S-benzyldithiocarbazate Schiff-base ligands were evaluated for their anti-Candida activity and their potential to disrupt the membrane architecture. The complexes displayed remarkable antifungal activity against a wide spectrum of fluconazole susceptible and resistant Candida albicans isolates, with Ni complex (dtc3) being highly active with minimum inhibitory concentration (MIC) values ranging from 1 to 32 µg/mL. Cell viability assay confirmed the fungicidal activity of these metal complexes, especially the complex dtc3. These metal complexes kill Candida albicans by inducing cellular apoptosis and necrosis thereby causing phosphatidylserine externalization as revealed by Annexin V-FITC and propidium iodide staining assays.

Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents.

Metal based drugs are important class of chemotherapeutic agents that have the potential to circumvent drug resistance. Increasing drug resistance, treatment failures and limited treatment options necessitates the development of new therapeutic drugs with different mechanisms of action. Towards this direction, we synthesized a series of isatin based mixed ligand complexes of [Cu(dbm)LClH2O] (mlc1), [Co(dbm)LCl2]‒ (mlc2) and [Ni(dbm)LClH2O] (mlc3) and evaluated their antifungal activity alone and in combination with fluconazole (FLC) against seven different Candida albicans isolates. The insight mechanism of antifungal action was revealed by studying apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The study revealed that all these compounds showed antifungal activity at varying concentrations with mlc3 as the most potent compound with minimum inhibitory concentration ranging from 0.5-8 µg/mL and minimum fungicidal concentration ranging from 4-16 µg/mL. Upon combination with FLC, most of the interactions were either synergistic (54 %) or additive (32 %) with no antagonistic combination against any of the tested isolate. The study on their mechanism of action revealed that these compounds show apoptotic effect on C. albicans at sub-inhibitory concentrations, suggesting that strategies to target this process may augment the current antifungal treatment modalities.

Probing the antibacterial and anticancer potential of tryptamine based mixed ligand Schiff base Ruthenium(III) complexes.

Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes [Ru(Cl)2(SB)(Phen] (RC-1) and [Ru(Cl)2(SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV-Vis, 1H, 13C NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of ≥250 µg/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV-Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481-1.015× 105 M-1. Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans.

BACKGROUND: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. METHODS: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. RESULTS: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. CONCLUSION: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

New transition metal complexes with a pendent indole ring: insights into the antifungal activity and mode of action.

Development of new chemotherapeutic agents to treat multidrug-resistant fungal infections to augment the current treatment options is a must. In this direction, a series of mixed ligand complexes was synthesized from a Schiff base (L) obtained by the condensation of 2-hydroxynapthaldehyde and tryptamine, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. Based on spectral characterization and physical measurements an octahedral geometry was assigned to [Co(phen)LClH2O] (C2), [Ni(phen)LClH2O](C3), and [Zn(phen)LClH2O](C4) complexes while a distorted octahedral geometry was assigned to the [Cu(phen)LClH2O](C1) complex. All the synthesized compounds were tested for antifungal activity against 11 Candida albicans isolates, including fluconazole (FLC) resistant isolates, by determining minimum inhibitory concentrations and studying growth curves. MIC results suggest that all the newly synthesized compounds have potent antifungal activity at varying levels. The rapid action of these compounds on fungal cells suggested a membrane-located target for their action.

Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy.

In recent years, the number of people suffering from cancer and multidrug-resistant infections has sharply increased, leaving humanity without any choice but to search for new treatment options and strategies. Although cancer is considered the leading cause of death worldwide, it also paves the way many microbial infections and thus increases this burden manifold. Development of small molecules as anticancer and anti-microbial agents has great potential and a plethora of drugs are already available to combat these diseases. However, the wide occurrence of multidrug resistance in both cancer and microbial infections necessitates the development of new and potential molecules with desired properties that could circumvent the multidrug resistance problem. A successful strategy in anticancer chemotherapy has been the use of metallo-drugs and this strategy has the potential to be used for treating multidrug-resistant infections more efficiently. As a class of molecules, Schiff bases have been the topic of considerable interest, owing to their versatile metal chelating properties, inherent biological activities and flexibility to modify the structure to fine-tune it for a particular biological application. Schiff base-based metallo-drugs are being researched to develop new anticancer and anti-microbial chemotherapies and because both anticancer and anti-microbial targets are different, heterocyclic Schiff bases can be structurally modified to achieve the desired molecule, targeting a particular disease. In this review, we collect the most recent and relevant literature concerning the synthesis of heterocyclic Schiff base metal complexes as anticancer and anti-microbial agents and discuss the potential and future of this class of metallo-drugs as either anticancer or anti-microbial agents.

Design, synthesis and spectroscopic characterization of metal (II) complexes derived from a tetradentate macrocyclic ligand: Study on antimicrobial and antioxidant capacity of complexes.

The paper presents the synthesis of Co(II), Ni(II) and Cu(II) complexes of macrocyclic Schiff base ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and ethyl 3-oxobutanoate (2:2). The synthesized ligand and its metal complexes were characterized by elemental analyses, magnetic susceptibility measurements, FTIR, UV-Vis., mass 1H NMR and X-ray diffraction. The Cu(II) complex exhibit distorted octahedral geometry, whereas an octahedral geometry is suggested for other complexes. The synthesized compounds were screened in vitro for their antimicrobial activities to evaluate their inhibiting potential against bacterial species Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and fungal species include Aspergillus flavus, Aspergillus fumingatus, and Candida albicans. The complexation led to a remarkable increase in antimicrobial activity. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals. The obtained IC50 value of the DPPH activity for the copper complex was higher than other compounds.

Design, synthesis, characterization and antimicrobial/antioxidant activities of 1, 4-dicarbonyl-phenyl-dihydrazide based macrocyclic ligand and its Cu(II), Co(II) and Ni(II) complexes.

Mononuclear transition metal complexes of Cu(II), Co(II) and Ni(II) with a newly synthesised macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and 1,2-diphenylethane-1,2-dione (2:2) have been synthesised. The synthesised compounds were characterised by various physical and spectroscopic techniques including elemental analysis, FTIR, Uv-Vis., 1H NMR, mass spectra, magnetic moment and XRD. The investigation of these macrocyclic complexes established that the stability of metal-ligand coordination through N atoms as tetradentate chelates. The metal/ligands ratio of 1:1 was proposed to afford octahedral geometry for the complexes. The antimicrobial activity of the compounds against some bacterial and fungal species were done by well diffusion method and the results shows that the metal complexes have a promising biological activity comparable with the parent ligand against all bacterial and fungal species. The antioxidant activity of the compounds was also studied through scavenging effect on DPPH radicals with the copper complex showing enhanced activity than other compounds. Additionally, the docking studies predicted the high antimicrobial activity due to the interaction of ligand with the protein.