| dc.description.abstract | The thesis consists of three parts, preceded by a general introduction to the malaria problem.
Introduction
In the introduction, the various aspects of the malaria problem have been dealt with, namely: the incidence of malaria, a brief historical development of the evolution of antimalarials, the discovery of Paludrine and its pharmacological and clinical trials, and other related problems, to provide the necessary background to the work described in Part I.
PART I
Chapter I
This deals with the synthesis of twenty four new biguanide derivatives of the type N¹ substituted aryl N [p nitro (or amino) benzenesulphonyl] biguanide.
The literature is full of reference to the versatility of sulphanilamides in combating many types of diseases. As the sulphonyl residue is responsible for the chemotherapeutic activity in the sulphanilamide type of compounds, it was thought worthwhile to explore further possibilities in the field of substituted biguanides as possible antimalarials, in order to discover a better drug.
The above compounds were prepared by reacting p nitrobenzenesulphonyl chloride with the various biguanides in acetone medium.
Four typical compounds have been tested pharmacologically against avian malaria, but none of them proved to be active.
Chapter II
This relates to the preparation and pharmacological examination of some new thiourea derivatives of sulphabiguanides of the type mentioned in Chapter I.
A reference to literature reveals thioureas, substituted or otherwise, as chemotherapeutically active compounds, being used as rodenticides and having activity in several bacterial infections. As the thioureido moiety is stated to possess chemotherapeutic properties, it was thought to be of interest to fuse this property with that of the sulphabiguanide chain, to obtain drugs of more potency and efficiency.
These compounds were prepared by reacting various mustard oils with the sulphabiguanide in alcohol-acetone medium.
None of the compounds tested had any antimalarial activity.
PART II
The work in this part deals with a new synthesis of 4,4’-diaminodiphenylsulphone (D.D.S.). Though with the advent of heterocyclic sulphanilamides as very potent antibacterials the sulphone receded into the background on account of its toxicity, it has come again into the limelight as a possible cure for tuberculosis, leprosy, and gas gangrene.
Lowe (Lancet, 1950, 255, 145) has described the successful treatment of leprosy by oral administration of D.D.S. in graded doses over a period of several months-a form of treatment that slowly accustoms the patient to larger doses previously considered too toxic. Some important derivatives of D.D.S. which give a significant degree of cure in tuberculosis are Promin, Diasone, and Sulphetrone. Thus, the parent sulphone is of enormous use in modern chemotherapy.
Barring one or two, the methods of synthesis of this sulphone are very tedious, involving many complicated stages with poor yields.
The new method of synthesis given in this part has two distinct advantages:
The method of preparation is easier, and
The yield is better than in previous methods.
According to this method, D.D.S. is prepared by condensing acetanilide with p acetamidobenzenesulphonyl chloride in the presence of aluminium chloride, using nitrobenzene as solvent.
PART III
This part deals with a new method of synthesis of p nitrobenzenesulphonyl chloride, which is a very important intermediate for the preparation of most of the sulpha drugs.
Although methods for the preparation of this compound are mentioned in literature, the purification is very tedious and the yields are low. Purification by distillation results in explosion in nine out of ten cases, even when carried out with utmost care. Crystallisation of the compound results in further loss.
The new method obviates all these difficulties, as the pure compound is obtained at the end of the reaction. p Nitrobenzenesulphonyl chloride is now prepared starting from sulphanilic acid. | |
