Subramani Kandhasamy

Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives

A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by (1)H NMR, (13)C NMR, Mass, IR and elemental analysis. All the compounds were evaluated for their anticancer activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the presence of electron donating group near sulphur enhanced the activity against HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g were the most active with IC50 values of 16, 12, 14 and 24.5 μM, respectively. The analogues were also screened for antimicrobial activity against two human bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA and antifungal activity against FRCA in well diffusion method.

Synthesis, characterization and biological evaluation of chromen and pyrano chromen-5-one derivatives impregnated into a novel collagen based scaffold for tissue engineering applications

In this article, we describe the synthesis and biological evaluation of a novel 2-(methylamino)-3-nitro-4-(4-oxo-4H-chromen-3-yl) pyrano[3,2-c]chromen-5(4H)-one (CCN). It is also determined that CCN impregnated into the collagen scaffold has the potential to mimic the function of the extracellular matrix as a biomaterial in the field of tissue engineering. The series of pyrano[3,2-c]chromen-5(4H)-one derivatives (4a–4j), was analyzed by 1H NMR, 13C NMR, mass spectra and FTIR analysis. Compound 4c was confirmed by single crystal XRD studies. All the compounds were screened for antimicrobial activity against Gram positive, Gram negative bacteria and yeast. Among all the compounds, compound (4aCCN) showed activity against Gram positive and Gram negative bacteria, when compared to the synthesized compounds. Further, compound CCN was evaluated for cytotoxicity against MCF-7, Hep-2 and Vero cancer cell lines with IC50 values of 5.4 μg ml−1, 5.3 μg ml−1 and 68.4 μg ml−1 respectively. In addition, the results of flow cytometry and docking (PDBID: 1A27 with the ligand) studies supported the activity of the synthesized compound (4a). FTIR and NMR analysis of the CCN impregnated collagen scaffold were done to reveal the existence of the CCN molecule in the scaffold. The inherent property of the collagen scaffold was not significantly affected by the structure of the CCN molecule. The thermal and mechanical properties of the collagen scaffold impregnated with CCN molecules gives stability as well as supports the swelling. However, the COL-CCN scaffold showed an enhanced cell attachment and proliferation of NIH 3T3 fibroblast cells. Based on the results, the novel CCN molecule impregnated within a collagen scaffold has potential application as a biomaterial in tissue engineering.

Synthesis and Fabrication of Collagen-Coated Ostholamide Electrospun Nanofiber Scaffold for Wound Healing

A novel scaffold for effective wound healing treatment was developed utilizing natural product bearing collagen-based biocompatible electrospun nanofibers. Initially, ostholamide (OSA) was synthesized from osthole (a natural coumarin), characterized by 1H, 13C, DEPT-135 NMR, ESI-MS, and FT-IR spectroscopy analysis. OSA was incorporated into polyhydroxybutyrate (PHB) and gelatin (GEL), which serve as templates for electrospun nanofibers. The coating of OSA-PHB-GEL nanofibers with collagen resulted in PHB-GEL-OSA-COL nanofibrous scaffold which mimics extracellular matrix and serves as an effective biomaterial for tissue engineering applications, especially for wound healing. PHB-GEL-OSA-COL, along with PHB-GEL-OSA and collagen film (COLF), was characterized in vitro and in vivo to determine its efficacy. The developed PHB-GEL-OSA-COL nanofibers posed an impressive mechanical stability, an essential requirement for wound healing. The presence of OSA had contributed to antimicrobial efficacy. These scaffolds exhibited efficient antibacterial activity against common wound pathogens, Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The zones of inhibition were observed to be 14 ± 22 and 10 ± 2 mm, respectively. It was observed that nanofibrous scaffold had the ability to release OSA in a controlled manner, and hence, OSA would be present at the site of application and exhibit bioactivity in a sustained manner. PHB-GEL-OSA-COL nanofiber was determined to be stable against enzymatic degradation, which is the most important parameter for promoting proliferation of cells contributing to repair and remodeling of tissues during wound healing applications. As hypothesized, PHB-GEL-OSA-COL was observed to imbibe excellent cytocompatibility, which was determined using NIH 3T3 fibroblast cell proliferation studies. PHB-GEL-OSA-COL exhibited excellent wound healing efficacy which was confirmed using full thickness excision wound model in Wistar rats. The rats treated with PHB-GEL-OSA-COL nanofibrous scaffold displayed enhanced healing when compared to untreated control. Both in vitro and in vivo analysis of PHB-GEL-OSA-COL presents a strong case of therapeutic biomaterial suiting wound repair and regeneration.

Evaluation of Stress-Induced Microbial Siderophore from Pseudomonas aeruginosa Strain S1 as a Potential Matrix Metalloproteinase Inhibitor in Wound Healing Applications

Abstract Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes capable of causing various inflammatory and various degenerative diseases if over-expressed. The active site of these enzymes is a zinc binding motif which binds to the specific site on the substrate and induce degradation. Hence an inhibitor is required to form a complex with zinc motif which hampers the binding ability of MMPs. To obtain novel MMPs inhibitor for wound healing, the chelating activity of siderophore from the microbial source was focused. During screening for siderophore production, strain S1 produced the highest amount of siderophore in the minimal salts medium. The isolate was confirmed as Pseudomonas aeruginosa strain S1 based on 16S rRNA gene sequencing and phylogenetic analysis. The activity of the siderophore was assayed using chrome azurol sulphonate and purified by the chromatographic techniques. The structural evidence through Fourier transform infrared and nuclear magnetic resonance spectra revealed that the isolated siderophore is a catecholate type with the distinctive characters. The positive results of calcein and fluozin-3 assays indicate that siderophore could bind to divalent metal ions, namely Fe2+ and Zn2+. As the siderophore compound focused on wound healing property, the in vitro studies revealed the viability of NH3T3 fibroblast cells and its efficiency in matrix modulating was confirmed through gelatin zymogram.

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a-5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.

Crystal structure of 2-methyl­amino-4-(6-methyl-4-oxo-4H-chromen-3-yl)-3-nitro­pyrano[3,2-c]chromen-5(4H)-one with an unknown solvate

In the title compound, C23H16N2O7, the mean planes of the two chromene units (r.m.s. deviations = 0.031 and 0.064 Å) are almost normal to one another with a dihedral angle of 85.59 (6)°. The central six-membered pyran ring has a distorted envelope conformation, with the methine C atom at the flap. There is an intramolecular N—H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(12) ring motif. The dimers are linked by pairs of C—H⋯O hydrogen bonds, enclosing R 2 2(6) ring motifs, forming zigzag chains along [001]. The chains are linked by a second pair of C—H⋯O hydrogen bonds, forming slabs parallel to (110). Within the slabs there are C—H⋯π interactions present. A region of disordered electron density was treated with the SQUEEZE procedure in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9–18] following unsuccessful attempts to model it as plausible solvent molecule(s). The given chemical formula and other crystal data do not take into account the unknown solvent molecule(s).

Crystal structure of 4-(6-bromo-4-oxo-4H-chromen-3-yl)-2-methyl­amino-3-nitro­pyrano[3,2-c]chromen-5(4H)-one chloro­form monosolvate

In the title compound, C22H13BrN2O7·CHCl3, the pyran ring adopts a shallow sofa conformation with the C atom bearing the bromochromene system as the flap [deviation = 0.291 (3) Å]. The dihedral angle between the pyran fused-ring system (all atoms; r.m.s. deviation = 0.032 Å) and the bromochromene ring system (r.m.s. deviation = 0.027 Å) is 87.56 (9)°. An intramolecular N—H⋯O hydrogen bond closes an S(6) ring. The Cl atoms of the solvent molecule are disordered over two sets of sites in a 0.515 (6):0.485 (6) ratio. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(12) loops. The packing also features C—H⋯O and very weak π–π [centroid–centroid separation = 3.960 (2) Å] interactions, which link the dimers into a three-dimensional network.

Crystal structure of 2-{[1-(4-bromo-benz-yl)-1H-1,2,3-triazol-4-yl]meth-oxy}naph-thalene-1,4-dione.

In the title compound, C20H14BrN3O3, the benzene ring makes dihedral angles of 71.30 (11) and 68.95 (14)° with the naphthalene ring system and the triazole ring, respectively. The latter two ring systems are coplanar, with a dihedral angle of 2.92 (12)°. The O atoms deviate from the naphthalene ring system by 0.029 (2) and −0.051 (2) Å. In the crystal, molecules are linked by C—H⋯O and C—H⋯N hydrogen bonds, forming ribbons parallel to (10-1). The ribbons are linked via C—H⋯O and π–π stacking interactions [centroid–centroid distance = 3.4451 (14) Å], forming slabs parallel to the bc plane.

Aza-Morita–Baylis–Hillman reaction of maleimides with azodicarboxylates under neat conditions

AbstractGreen approach on reaction of diisopropylazodicarboxylate or diethyl azodicarboxylate with maleimides proceeded smoothly under neat condition at 70°C to give the corresponding hydrazine substituted pyrrolidinone as aza-Morita–Baylis–Hillman adducts in moderate to good yields in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as nitrogen Lewis base. Graphical AbstractGreen approach on reaction of diisopropylazodicarboxylate or diethyl azodicarboxylate with maleimides proceeded smoothly under neat condition at 70oC to give the corresponding hydrazine substituted pyrrolidinone as aza-Morita–Baylis–Hillman adducts in moderate to good yields in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as nitrogen Lewis base.