Gul Shahzada Khan

Chemistry of DNA minor groove binding agents

Most of the clinically used anticancer drugs exert their antitumor effect by damaging the replication machinery of DNA either by covalent or non-covalent binding. Intercalation and groove fitting are the major modes of non-covalent interaction. Small crescent shaped molecules have been claimed to bind with DNA via minor grooves. A plethora of hybrid molecules based on distamycin or netropsin have been synthesised with the objectives of improved selectivity and specificity with no/reduced unwanted side effects. This review critically and objectively describes the previously known hybrid DNA minor groove binding agents based on five membered, distamycin or netropsin. Moreover, the future use of six-membered benzamides has also been highlighted. Special emphasis has been put on developing structure-activity relationships of DNA minor groove binding agents.

Micelles as Soil and Water Decontamination Agents

Contaminated soil and water pose a serious threat to human health and ecosystem. For the treatment of industrial effluents or minimizing their detrimental effects, preventive and remedial approaches must be adopted prior to the occurrence of any severe environmental, health, or safety hazard. Conventional treatment methods of wastewater are insufficient, complicated, and expensive. Therefore, a method that could use environmentally friendly surfactants for the simultaneous removal of both organic and inorganic contaminants from wastewater is deemed a smart approach. Surfactants containing potential donor ligands can coordinate with metal ions, and thus such compounds can be used for the removal of toxic metals and organometallic compounds from aqueous systems. Surfactants form host-guest complexes with the hydrophobic contaminants of water and soil by a mechanism involving the encapsulation of hydrophobes into the self-assembled aggregates (micelles) of surfactants. However, because undefined amounts of surfactants may be released into the aqueous systems, attention must be paid to their own environmental risks as well. Moreover, surfactant remediation methods must be carefully analyzed in the laboratory before field implementation. The use of biosurfactants is the best choice for the removal of water toxins as such surfactants are associated with the characteristics of biodegradability, versatility, recovery, and reuse. This Review is focused on the currently employed surfactant-based soil and wastewater treatment technologies owing to their critical role in the implementation of certain solutions for controlling pollution level, which is necessary to protect human health and ensure the quality standard of the aquatic environment.

Photochemistry and electrochemistry of anticancer uracils.

The redox mechanism and electronic absorption behavior of a commercial anticancer drug, 5-fluorouracil (5-FU) and two potential anticancer drugs, 2-thiouracil (2-TU) and dithiouracil (DTU) have been investigated in a wide pH range by UV-Vis spectroscopy, cyclic voltammetry and differential pulse voltammetry. The effect of electrolytes, substituents, successive sweeps and potential scan rate on the voltammetric response of uracils was examined. Organized structure-activity relationships of these drugs were established on the basis of the results obtained from electronic absorption spectroscopy and cyclic voltammetry. The electrode reaction mechanism was suggested using the experimentally determined electrochemical parameters. The DNA binding propensity of uracils was found greater than the classical intercalator, proflavin and clinically used drug, epirubicin. Moreover, the results obtained through ab initio calculations for the oxidation potential of the three uracil derivatives were found in good agreement with the electrochemical results.

Synthesis, spectroscopic characterization, pH dependent redox mechanism and DNA binding behavior of chlorohydroxyaniline derivatives

The derivatives of anilines are promisingly useful in rechargeable batteries, electrochromics and biosensors. Phenol and aniline based compounds are bestowed with strong antioxidant and anticancer activities. Based on these considerations three new chlorohydroxyanilines (CHAs) were synthesized and characterized by IR, 13C NMR, 1H NMR and UV-Vis spectroscopy. Cyclic, differential pulse and square wave voltammetry were used for the investigations of the electrochemical fate of these compounds in different pH media. Computational chemistry was used as a tool to verify the experimental outcomes. Two chlorohydroxyanilines were found to oxidize at a potential lower than the standard antioxidant, ascorbic acid. The pH dependent oxidation indicated the involvement of protons during electron transfer reactions. The quasi-reversible and irreversible nature of the first and second oxidation peak was evidenced by square wave voltammetry. The slope of peak potential vs. pH plot and the width at half peak height indicated 1e and 1H+ involvement in each oxidation step. Molecular docking and UV-Vis spectroscopy revealed that all chlorohydroxyanilines interact with DNA via an electrostatic binding mode. A sensitive differential pulse technique allowed the determination of a very low limit of detection.

Synthesis and biological activity of benzamide DNA minor groove binders.

A range of di- and triaryl benzamides were synthesised to investigate the effect of the presence and nature of a polar sidechain, bonding and substitution patterns and functionalisation of benzylic substituents. These compounds were tested for their antiproliferative activity as well as their DNA binding activity. The most active compounds in all assays were unsymmetrical triaryl benzamides with a bulky or alkylating benzylic substituent and a polar amino sidechain.

Synthesis and characterization of monoaryl esters of l -tartaric acid and their process for fries rearrangement

Chiral protected monoaryl esters (2a–2h) were synthesized from monoester of l-tartaric acid, having two asymmetric centers and C2 axis of symmetry. l-tartaric acid was protected and partially hydrolyzed to give the corresponding monoester. Monoester upon treatment with different substituted phenols gave desired monoaryl esters (2a–2h). Fries rearrangement of monoaryl esters was then tried under various conditions by using different Lewis acids. All the compounds were purified and characterized by using spectroscopic techniques like IR, 1H-NMR, 13C-NMR, HRMS-ESI, and elemental analysis. The structure of compound 2e was obtained by X-ray crystallography.

3,5-Dinitro-benzyl methane-sulfonate.

The title compound, C8H8N2O7S, an intermediate in the synthesis of N,N-bis(2-hydroxyethyl)-3,5-dinitroaniline, exists as a discrete molecule; the nitro groups are twisted with respect to the aromatic system [dihedral angles = 17.0 (1) and 26.3 (1)°].

2,2′-(3,5-Dinitro­benzyl­imino)diethanol

The title compound, C11H15N3O6, was prepared by the reaction of (3,5-dinitrobenzyl)methanesulfonate with diethanolamine. The asymmetric unit contains four crystallographically independent molecules which differ primarily in their rotation about the bond between the aromatic ring and the N-diethanol unit. The molecules are linked into sheets by a hydrogen-bonding network which involves all of the hydroxy groups, with only van der Waals contacts between the sheets.

N-{3-[Bis(2-hydroxy­ethyl)amino­meth­yl]-5-nitro­phen­yl}benzamide

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitrobenzyl methanesulfonate with diethanolamine and is an intermediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent molecules, which differ only in the orientations of the hydroxyethyl groups. In the crystal structure, intermolecular N—H⋯O and O—H⋯O hydrogen bonds link molecules into one-dimensional chains.

N-[3-(tert-Butyl­dimethyl­siloxymeth­yl)-5-nitro­phen­yl]acetamide

The title compound, C15H24N2O4Si, was prepared by the reaction of (3-acetamido-5-nitrobenzyl)methanol with tert-butyldimethylsilyl chloride and is a key intermediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent molecules in the structure, which differ primarily in the rotation about the C—O bond next to the Si atom. Two strong N—H⋯O hydrogen bonds align the molecules into a wide ribbon extending approximately parallel to the b axis.