Zahid Yaseen

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).

Modulation of bovine serum albumin fibrillation by ester bonded and conventional gemini surfactants

Protein fibrillation has been associated with various neurological disorders. Knowledge about molecular mechanisms of protein aggregation modulators is potentially helpful for therapeutic purposes. In order to find out the key strategies for promotion and inhibition of protein fibrillation and to create better functional designs, we have studied the effect of gemini surfactants on the bovine serum albumin fibrillation. The ThT fluorescence emission spectrum indicates disintegration of BSA fibrils in presence of m-C2-m gemini surfactants (conventional). However, enhancement in BSA fibril formation takes place in presence of m-E2-m diester bonded gemini surfactants. Although, with increase in tail length of m-E2-m gemini surfactant, slight disintegration of fibrils also occurs. Circular dichroism data suggest decrease in the β-content of the BSA fibrils in presence of m-C2-m surfactant, while as increase in β-content of fibrils in presence of m-E2-m surfactant. FTIR, TEM, and confocal microscopic results also show that m-C2-m disintegrates and m-E2-m prompts the fibrillation. The electrostatic/hydrogen bonding/hydrophobic balance play important roles in determining the BSA fibrillation and disintegration. Micelles of m-C2-m surfactants disrupt the hydrogen bonding in between the β-strands, hence result in fragmented fibrils. Presence of diester group in m-E2-m surfactant forms hydrogen bonds in between the β-strands resulting in enhancement of fibril formation.

In vitro cytotoxcity and interaction of new steroidal oxadiazinanones with calf thymus DNA using molecular docking, gel electrophoresis and spectroscopic techniques

Herein we report synthesis of new steroidal oxadiazinanones from steroidal ketones. After characterization by spectral and analytical data, the interaction studies of compounds (4-6) with DNA were carried out by UV-vis, fluorescence spectroscopy and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 1.8×10(4) M(-1), 2.2×10(4) M(-1) and 2.6×10(4) M(-1), respectively, indicating the higher binding affinity of compound 6 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compound 6 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. Molecular simulations suggest that compounds binds through minor groove of DNA. MTT assay depicted promising anticancer activity of compound 5 and 6 particularly against HL-60 and MCF-7. The apoptotic degradation of DNA was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). The results revealed that compound 6 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

Recent review for removal of metal ions by hydrogels

ABSTRACT A continuous research is going to synthesize the novel adsorbents for removal of toxic metal ions having high sorption capacity along with non-toxic and biodegradable nature. Ionic impurities have been removed in many ways. However, hydrogels with high sorption capacity, high functionality, hydrophilicity, regeneration and nontoxicity have made them a good contender for the removal of various aquatic pollutants, including heavy metal ions. Moreover, certain modifications in synthesis of hydrogels, to customize them in response to different stimuli like temperature, pH and ionic strength, has added an advantage in waste water treatment. The present review provides recent progress in the synthesis of the hydrogels for waste water treatment and insight into increase in selectivity, efficiency and reusability of hydrogels.

Morphological changes in human serum albumin in presence of cationic amphiphilic drugs

Human serum albumin (HSA) is one of the most important carrier proteins present in the blood and can constitute more than half of serum proteins. It transports various biomolecules including hormones, fatty acids, ions, drugs and functions to regulate oncotic pressure in the plasma. Cationic amphiphillic drugs like amitriptyline hydrochloride, imipramine hydrochloride and promethazine hydrochloride bind to HSA and influences function by altering its conformation, as confirmed by Small-angle neutron scattering (SANS) data coupled to dynamic light scattering measurements (DLS). Protein unfolding was observed by SANS results through an increase in the value of the radius of gyration Rg. At higher drug concentrations, there was no change in the dimensions of the protein. However, the drugs formed free aggregates at higher concentrations without any growth in the drug micelles, which was confirmed by the appearance of second peak in DLS measurements. Molecular docking revealed that the morphology of hydrophobic moiety of the cationic amphiphilic drugs decides their binding fate with HSA, while trajectories from molecular dynamics simulations highlight structural disorder in the drug-HSA complex.