Mahboob Alam

Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba

OBJECTIVES The present study focused on isolation, characterization and evaluation of purified compounds from Morus alba against Streptococcus mutans biofilm formation. METHODS The effect of crude extract from M. alba leaves was evaluated against oral pathogens, chiefly S. mutans. MICs were determined by the microdilution method. The compound was purified by employing silica gel chromatography and critically analysed with GC-MS, NMR and IR spectroscopy. The S. mutans traits of adherence and biofilm formation were assessed at sub-MIC concentrations of the crude extract and purified compound. Both water-soluble and alkali-soluble polysaccharide were estimated to determine the effect of the purified compound on the extracellular polysaccharide secretion of S. mutans. Its effect on biofilm architecture was also investigated with the help of confocal microscopy. RESULTS The purified compound of M. alba showed an 8-fold greater reduction of MIC against S. mutans than the crude extract (MICs, 15.6 and 125 mg/L, respectively). The extract strongly inhibited biofilm formation of S. mutans at its active accumulation and plateau phases. The purified compound led to a 22% greater reduction in alkali-soluble polysaccharide than in water-soluble polysaccharide. The purified compound was found to be 1-deoxynojirimycin (DNJ). Confocal microscopy revealed that DNJ distorts the biofilm architecture of S. mutans. CONCLUSIONS The whole study reflects a prospective role of DNJ as a therapeutic agent by controlling the overgrowth and biofilm formation of S. mutans.

In vitro DNA binding, molecular docking and antimicrobial studies on a newly synthesized poly(o-toluidine)–titanium dioxide nanocomposite

A poly(o-toluidine)–titanium dioxide (POT–TiO2) nanocomposite has been synthesized for the first time by in situ chemical oxidative polymerization of o-toluidine (OT) in the presence of titanium dioxide (TiO2) nanoparticles. FTIR, SEM, TEM, XRD, TGA and DTA were used to characterize the POT–TiO2 nanocomposite. The characterization results confirmed that there is a strong interaction between POT and TiO2 nanoparticles and the nanocomposite showed higher thermal stability than pristine POT. The in vitro DNA binding studies of POT and POT–TiO2 nanocomposite with ct-DNA in physiological buffer (pH-7.4) were investigated using spectrophotometry and circular dichroism. The absorption spectra of the POT and POT–TiO2 nanocomposite with DNA showed a hypochromic effect. The four types of 3D molecular field descriptors or field points as extrema of electrostatic, steric, and hydrophobic fields are described. These field points are used to define the properties necessary for a molecule to bind in a characteristic way into a specified active site. A molecular docking simulation was used to predict the modes of interactions of the drugs (POT and POT–TiO2) with DNA. The molecular docking results indicated that the modes of interactions between the two (POT and POT–TiO2) and DNA helix can be considered as groove binding. Moreover, the comparative antimicrobial activities of POT and its POT–TiO2 nanocomposite were tested and were found to exhibit antibacterial activity against Gram positive as well as Gram negative bacterial strains at micromolar concentration.

Synthesis and characterization of novel PUFA esters exhibiting potential anticancer activities: An in vitro study

Polyunsaturated fatty acids (PUFAs) have been reported to play a regulatory role in tumour growth progression. In the present study, we have synthesized ester derivatives of two important PUFA viz., linoleic acid (LA) and arachidonic acid (AA) with propofol, a widely used general anaesthetic-sedative agent. The novel propofol ester analogues have been found to inhibit various cancer cell lines in a dose-dependent manner. Moreover, the compounds have been found to induce apoptotic cell death by enhancing the release of cytochrome c and expression of caspase-3. The data of the present study suggest that novel propofol-PUFA esters have strong potential to emerge as effective anticancer agents.

Enzyme immobilization and molecular modeling studies on an organic–inorganic polypyrrole–titanium(IV)phosphate nanocomposite

In this work we report the synthesis of an electrically conductive polypyrrole–titanium(IV)phosphate (PPy–TiP) nanocomposite using simple, facile in situ chemical oxidative polymerization of polypyrrole (PPy) in the presence of titanium(IV)phosphate (TiP) for immobilization of the yeast alcohol dehydrogenase enzyme. FTIR, FE-SEM and TGA were employed for the characterization of PPy, TiP and the PPy–TiP nanocomposite. YADH was successfully immobilized on the PPy–TiP nanocomposite with a loading efficiency of 69%. The immobilized YADH showed no change in the pH optima (pH 8.0) and there was a broadening of the peak both at acidic as well as in alkaline pH. The optimum temperature of immobilized YADH was increased by 5 °C with almost the same residual activity. Immobilized YADH showed improved thermal stability at 60 °C and retained about 71% activity after 5 h of incubation. Also, the immobilized YADH showed greater reusability and retained 75% activity after 10th successive use. All the results were compared to those of free YADH, immobilized YADH on PPy and immobilized YADH on TiP. The affinity of immobilized YADH for ethanol was decreased as evident from the Km value (223.71 mM) and also there was a decrease in the maximum velocity (201.53 μM min−1) as compared to soluble YADH. The improved residual activity, stability and reusability of YADH immobilized on the PPy–TiP nanocomposite make the enzyme more suitable for industry-based applications. Molecular docking was used to query the protein – the newly synthesized chemical entity interactions that help in understanding the affinity in enzyme activity.

Synthesis, characterization, DNA-binding studies and acetylcholinesterase inhibition activity of new 3-formyl chromone derivatives.

A series of new substituted 3-formyl chromone derivatives (4-6) were synthesized by one step reaction methodology by knoevenagel condensation, structurally similar to known bisintercalators. The new compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and analytical data. The in vitro DNA binding profile of compounds (4-6) was carried out by absorption, fluorescence and viscosity measurements. It was found that synthesized compounds, especially compound 6 (evident from binding constant value) bind strongly with calf thymus DNA, presumably via an intercalation mode. Additionally, molecular docking studies of compounds (4-6) were carried out with B-DNA (PDBID: 1BNA) which revealed that partial intercalative mode of mechanism is operational in synthesized compounds (4-6) with CT-DNA. The binding constants evaluated from fluorescence spectroscopy of compounds with CT-DNA follows the order compound 6>compound 5>compound 4. All the compounds (4-6) were screened for acetylcholinesterase inhibition assay. It can be inferred from data, that compound (6) showed potent AChE inhibition having IC50=0.27μM, almost in vicinity to reference drug Tacrine (IC50=0.19μM).

Interaction mode of polycarbazole–titanium dioxide nanocomposite with DNA: Molecular docking simulation and in-vitro antimicrobial study

A polycarbazole-titanium dioxide (PCz/TiO2-8) nanocomposite was synthesized for the first time by in-situ oxidative polymerization with APS as an oxidizing agent in the presence of TiO2 nanoparticles which was characterized by SEM, TEM, FT-IR, DTA and TGA techniques. The SEM and TEM results showed that PCz has polymerized on the surface of the TiO2. The results confirmed the incorporation of TiO2 in PCz indicating the formation of nanocomposite due to strong interaction between TiO2 and PCz matrix affecting the properties as compared to pristine PCz. The PCz/TiO2-8 nanocomposite was tested for antimicrobial activity and found to exhibit activity against gram negative and gram positive strains at micromolar concentrations. The four types of 3D molecular field descriptors or field points as extrema of electrostatic, steric, and hydrophobic fields were explained. These field points were used to define the properties necessary for a molecule to bind in a characteristic way into a specified active site. A molecular docking simulation was used to predict the modes of interactions of the drugs (PCz and PCz/TiO2-8) with DNA. The molecular docking conclusion indicated that the modes of interactions between two (PCz and PCz/TiO2-8) and DNA helix can be regarded as minor groove binder. The K value (3.55 × 10(4) M(-1) and 2.13 × 10(5) M(-1)) obtained from fluorescence data are indicative of binding of PCz and PCz/TiO2-8 with DNA helix.

Two new phenolic compounds from Ficus rumphii and their antiproliferative activity

Two new compounds 2 and 4, along with two known compounds 1 and 3, were isolated for the first time from 95% ethanolic extract of the leaves of Ficus rumphii. Their structures were elucidated on the basis of chemical and physical evidences (elemental analysis, UV, IR, 1H NMR, 13C NMR and mass spectra) and comparison with the literature compounds. Structural authentication of compound 4 was further validated by single-crystal X-ray analysis and DFT calculations. The compounds 1–4 were screened for in vitro cytotoxicity against cancer and non-cancer cells and also tested for genotoxicity (comet assay). Compounds 2 and 4 displayed significant activity against HL-60 with IC50 values of 3.3 and 2.3 μM, respectively. The results revealed that compound 4 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

Synthesis, characterization, thermal and antioxidant studies of potassium dihydrobisphenothiazinyl borate and its transition metal complexes

The bidentate borate anion H(2)B(ptz)(2)(-) and its transition metal complexes have been synthesized and characterized by elemental analyses, magnetic susceptibility, electronic, IR, (1)H and (13)C NMR data. The molar conductance of 10(-3) M solution for all the complexes supports their non-ionic nature. The TGA profile of borate anion shows a single stage unlike that of two stage decomposition plot of the metal complexes. On the basis of spectroscopic studies the geometry of all the complexes have been proposed to be distorted-tetrahedral. The in vitro antioxidant and lipid oxidation inhibition of the ligand and its complexes have also been studied. The Cu[B(ptz)(2)](2) complex was found to be most effective in all the studies.

[Et3NH][HSO4]-catalyzed eco-friendly and expeditious synthesis of thiazolidine and oxazolidine derivatives

The present study reports a facile and green approach for the synthesis of thiazolidine/oxazolidine derivatives 4(a–u) in excellent yields (92–98%) with high purity. The protocol involves a one-pot three-component reaction of substituted 1,3-diketones 1(a–g), cyanates 2(a–c) and ethylchloroacetate (3) in ionic liquid [Et3NH][HSO4] under solvent-free conditions. The notable feature of this pathway is that the ionic liquid possesses both catalytic as well as medium engineering capability in this protocol. Use of [Et3NH][HSO4] as a catalyst and an environmentally benign solvent eliminates the need for a volatile organic solvent and additional catalyst. This ionic liquid is air and water stable and easy to prepare from cheap amine and acid. The present synthetic route is a green protocol offering several advantages, such as excellent yield of products, mild reaction conditions, minimizing chemical waste, shorter reaction time, simple operational procedure, easy preparation of the catalyst and its recyclability up to five cycles without any noticeable loss in catalytic activity. The protocol is applicable to a broad substrate scope. The optimization of conditions carried out in the present study revealed that 20 mol% of ionic liquid catalyst under solvent-free conditions at 120 °C are the best reaction parameters for the synthesis of thiazolidine/oxazolidine derivatives in excellent yields.

Stereoselective synthesis of Z-acrylonitrile derivatives: catalytic and acetylcholinesterase inhibition studies

In the present study, a focused library of (Z)-acrylonitrile analogues (library A & B) were synthesized, which were typically accessed via a facile Knoevenagel condensation between p-nitrophenylacetonitrile and appropriately substituted aromatic aldehydes (1a–i) and 3-formyl chromones (3a–c). This new synthetic eco-friendly approach resulted in a remarkable improvement in the synthetic efficiency (83–92% yield), high purity, minimizing the production of chemical wastes without using highly toxic reagents for the synthesis and, more notably, it improved the selectivity for (Z)-acrylonitrile derivatives. By performing DFT calculations, it was found that the (Z)-isomer of compound 2b is stabilized by 2.61 kcal mol−1 more than the (E)-isomer. All of the compounds were tested for acetylcholinesterase (AChE) inhibition. Compounds 2a and 4c, displayed the strongest inhibition, with IC50 values of 0.20 μM and 0.22 μM respectively. The methoxy group at the para-position of phenyl ring A was found to be essential for AChE inhibition.