History as Profession and as Political Capital

History comes to us from various agencies not just academics in schools and colleges; but diverse inputs to all those who haven’t studied history, like popular history, through cinema, poetry, folklore, myths, theatre; history has several modes of percolation to society. Also, a kind of history is propagated in an organised manner as is done by organisations as RSS which is a practical approach to history as differentiated from an academic approach to history; the former is more political than the latter though both come with an aspect of politics. History thus has much wider reach than what is taught in schools or colleges.

Selective Degradation and Oxidation of Hydroxyethyl Starch for Immobilization of Some Antidiabetic Drugs

The low solubility and permeability of drugs, in general, leads to unsatisfactory pharmacokinetics profile of drugs. Polymer conjugation has attracted increasing interest in pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. The objective of this work was to find a method to overcome the solubility and permeability problems using the conjugation strategy. In this regard, hydroxyethyl starch (HES), a highly biocompatible semi-synthetic biopolymer, was used as a drug carrier. N- Arylsulfonylbenzimidazolones were selected as antidiabetic compounds of choice for coupling with HES. The experiments established the viability of a covalent coupling between polymer and N-arylsulfonylbenzimidazoles using a suitable coupling strategy. As a requirement for the desired coupled products, HES must have Mw that is suitable for drug delivery and excretion through the kidney. Therefore, HES needs to undergo a selective degradation. In the present study, two different methods for hydrolysis, i.e. acidic and enzymatic, were used for selective degradation of HES. It was found that the enzymatic hydrolysis method is superior to acidic hydrolysis. The enzymatic method was used to obtain HES of Mw as low as ≈ 10,000 g/mol. The selectively degraded HES was oxidized to generate carboxylic acid groups at the chain ends to serve as a coupling site for N-arylsulfonylbenzimidazolones, the selected antidiabetic compounds. For oxidation of HES, potassium permanganate and sodium oxychloride were tried as oxidizing agents. The sodium oxychloride method was found advantageous over permanganate method. The degraded and oxidized products were characterized using GPC, IR and NMR techniques. N-Arylsulfonylbenzimidazolones were synthesized using a multistep sequence to serve as antidiabetic compounds. The structures of all the synthesized arylsulfonylbenzimidazolne products and intermediates were established using spectroscopic techniques and the purity ascertained by elemental analysis. The synthesized arylsulfonylbenzimidazolnes were coupled to oxidized HES of molecular weights 17,490 g/mol and 10,067 g/mol by creating an amide linkage between the two units. iiThe coupled products were characterized using GPC, IR, 1 H NMR and 13 C NMR spectroscopy. The coupled products were screened for their antidiabetic potential on male albino rats of the Sprague–Dawley albino family at a dose of 20 mg and 40 mg per Kg body weight of the rats. It was observed that all the synthesized compounds were highly active. 2,3-Dihydro-3-(4- nitrobenzensulfonyl)-2-oxo-1H-benzimidazole (63) was found most potent with a 54 % reduction in blood glucose level of the rats as compared to 41 % reduction produced by tolbutamide and 38 % by glucophage. The coupling of these antidiabetic compounds with oxidized HES resulted in an increase of the hypoglycemic activity of all the compounds. The activity of compound 63 on coupling to HES 10,067 increased to 67 % reduction in blood glucose level.