Shravankumar Kankala

Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their in vivo analgesic and anti-inflammatory activity studies.

Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their efficiency in in vivo analgesic and anti-inflammatory activity was described. A comparison of structure-activity relationship for there compounds was also emphasized.

Utilization of Enzyme-Immobilized Mesoporous Silica Nanocontainers (IBN-4) in Prodrug-Activated Cancer Theranostics

To develop a carrier for use in enzyme prodrug therapy, Horseradish peroxidase (HRP) was immobilized onto mesoporous silica nanoparticles (IBN-4: Institute of Bioengineering and Nanotechnology), where the nanoparticle surfaces were functionalized with 3-aminopropyltrimethoxysilane and further conjugated with glutaraldehyde. Consequently, the enzymes could be stabilized in nanochannels through the formation of covalent imine bonds. This strategy was used to protect HRP from immune exclusion, degradation and denaturation under biological conditions. Furthermore, immobilization of HRP in the nanochannels of IBN-4 nanomaterials exhibited good functional stability upon repetitive use and long-term storage (60 days) at 4 °C. The generation of functionalized and HRP-immobilized nanomaterials was further verified using various characterization techniques. The possibility of using HRP-encapsulated IBN-4 materials in prodrug cancer therapy was also demonstrated by evaluating their ability to convert a prodrug (indole-3-acetic acid (IAA)) into cytotoxic radicals, which triggered tumor cell apoptosis in human colon carcinoma (HT-29 cell line) cells. A lactate dehydrogenase (LDH) assay revealed that cells could be exposed to the IBN-4 nanocomposites without damaging their membranes, confirming apoptotic cell death. In summary, we demonstrated the potential of utilizing large porous mesoporous silica nanomaterials (IBN-4) as enzyme carriers for prodrug therapy.

Multi-laminated metal hydroxide nanocontainers for oral-specific delivery for bioavailability improvement and treatment of inflammatory paw edema in mice

Multiple layers of pH-sensitive enteric copolymers were coated over layered double hydroxide (LDH) nanoparticles for controllable drug release and improved solubility of hydrophobic drugs. The nano-sized LDH carriers significantly improved the accessibility of sulfasalazine molecules that have positively charged frameworks. In addition, the successful encapsulation of negatively charged enteric copolymers was achieved via electrostatic attractions. The multi-layered enteric polymer coating could potentially protect nanoparticle dissolution at gastric pH and accelerate the dissolution velocity, which would improve the drug bioavailability in the colon. Next, biological studies of this formulation indicated a highly protective effect from the scavenging of superoxide free radicals and diethyl maleate (DEM) induced lipid peroxidation, which are major cell signalling pathways for inflammation. The histological view of the liver and kidney sections revealed that the nanoformulation is safe and highly biocompatible. The animal studies conducted via paw inflammation induced by complete Freunds adjuvant (CFA) revealed that enteric-coated LDH-sulfasalazine nanoparticles provided a sustained release that maintained the sulfasalazine concentrations in a therapeutic window. Therefore, this nanoformulation exhibited preferential efficacy in reducing the CFA-induced inflammation especially at day 4.

Synthesis of Markovnikov vinyl sulfides via dinuclear Rh(I)-phosphine catalyzed hydrothiolation of alkynes in aqueous media

An efficient and green procedure for the synthesis of Markovnikov i.e. branched vinyl sulfides in aqueous media was developed by employing the dinuclear Rh(I) complexes of hydrophilic phosphines as catalysts in the alkyne hydrothiolation with aliphatic thiols. Deuterium-labeling studies provide evidence for the aptness of these dinuclear catalysts to form selectively the Markovnikov syn-addition products. Catalyst order experiments disclose that the order with respect to the concentration of the catalyst is one, i.e. in solution the active catalyst is dinuclear with one active metal center and the second metal center contribute the cooperative effects to influence the Markovnikov selectivity in hydrothiolation. Further, the possibility of catalyst recovery and recycling experiments were also demonstrated.

Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene–alkaloids and their anti-cancer evaluation

A facile synthesis of piperidine alkene-alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene-alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.

Synthesis characterization and hydroformylation activity of new mononuclear rhodium(I) compounds incorporated with polar-group functionalized phosphines

A first effort employing a range of polar-group functionalized phosphines (L1–L7) to design mononuclear Rh(I) compounds of [Rh(quin-8-O)(CO)(L)] (quin-8-O = 8-hydroxy quinolate) is described. The reaction of a Rh(I) precursor [Rh(μ-Cl)(CO)2]2 with 8-hydroxyquinoline in the presence of a base followed by phosphines (L1–L7) produced only a single isomer of [Rh(quin-8-O)(CO)(L)] compounds (1–7) with pendant, i.e. non-bonded, polar-groups (includes carboxyl, hydroxyl and formyl). A relationship between Δgd31P chemical shifts and the ν(C≡O) was derived to evaluate and explain the σ-donor properties of these phosphines with respect to the electronic properties of the polar groups and the extent of π-back-bonding to the CO group. These mononuclear Rh(I)-Phosphines were investigated as catalysts in the hydroformylation of 1-hexene and cyclohexene in aqueous two-phase and single-phase solvent systems. The Rh(I) catalysts with strong σ-donor and hydrophilic phosphines provided better yields and selectivities for the hydroformylation products, which is a reverse trend compared to literature reports. When the Rh(I) compounds contained strong σ-donor phosphines, the π-acceptor properties of the pyridine ring of 8-hydroxyquinolate were found to be beneficial for the facile cleavage of the CO group during hydroformylation, and additionally, to improve the kinetic stability of catalysts.

Regioselective synthesis of some new 1,4-disubstituted sulfonyl-1,2,3-triazoles and their antibacterial activity studies

Some new 1,4-disubstituted-sulfonyl-1,2,3-triazoles (3a–f, 5a–h, 7a–d, and 9a–e) were regioselectively synthesized in high yields by Cu(I) catalyzed 1,3-dipolar cycloaddition (DC) reaction of p-acetamidobenzenesulfonyl azide (p-ABSA) with terminal alkynes. These new triazole compounds were evaluated for in vitro antibacterial activity against a panel of Gram-positive Bacillus sphericus, Staphylococcus epidermidis, and Gram-negative Klebsiella pneumonia, Escherichia coli species. Several of these compounds were found to possess comparable growth inhibition activity with the commercial standards Penicillin-G and Streptomycin.

Zinc-catalyzed multicomponent reactions: Facile synthesis of fully substituted pyridines

Abstract A first example of environmentally benign zinc complex catalyzed one-pot four-component reaction between malononitrile, ketone, ammonium acetate and aromatic aldehyde for the facile synthesis of fully substituted pyridines just within 2 min in environmentally friendly solvent ethanol has been optimized. GRAPHICAL ABSTRACT

Synthesis and Antibacterial Studies of Schiff bases derived from o-phthalaldehyde

A series of twelve new azomethine derivatives were synthesized by the condensation of o-phthalaldehyde with primary amine derivatives. The chemical structures of these compounds were confirmed by IR, 1H, 13C NMR, Mass and elemental analysis. Antibacterial activities of these compounds have been tested against four strains of bacteria (Bacillus subtillus, Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia) and found to possess potential antibacterial activity.