%0 Journal Article
%T Sulfonamide Based ¦Â-Carbonic Anhydrase Inhibitors: 2D QSAR Study
%A Meenakshi N. Deodhar
%A Priyanka L. Khopade
%A Mahesh G. Varat
%J ISRN Medicinal Chemistry
%D 2013
%R 10.1155/2013/107840
%X The carbonic anhydrases (CAs) (or carbonate dehydratases) form a family of metalloenzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa), a reversible reaction that occurs rather slowly in the absence of a catalyst. The ¦Â-CAs have been characterized in a high number of human pathogens, such as the fungi/yeasts Candida albicans, Candida glabrata, Cryptococcus neoformans, and Saccharomyces cerevisiae and the bacteria Helicobacter pylori, Mycobacterium tuberculosis, Haemophilus influenzae, Brucella suis, and Streptococcus pneumonia. The ¦Â-CAs in microorganisms provide physiological concentration of carbon dioxide and bicarbonate (CO2/ ) for their growth. Inhibition of ¦Â-CAs from the pathogenic microorganism is recently being explored as a novel pharmacological target to treat infections caused by the these organisms. The present study aimed to establish a relationship between the ¦Â-CAs inhibitory activity for structurally related sulphonamide derivatives and the physicochemical descriptors in quantitative terms. The statistically validated two-dimensional quantitative structure activity relationship (2D QSAR) model was obtained through multiple linear regression (MLR) analysis method using Vlife molecular design suits (MDS). Five descriptors showing positive and negative correlation with the ¦Â-CAs inhibitory activity have been included in the model. This validated 2D QSAR model may be used to design sulfonamide derivatives with better inhibitory properties. 1. Introduction The CAs belong to the family of metalloenzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa), a reversible reaction that occurs rather slowly in the absence of a catalyst. The active site of most carbonic anhydrases contains a zinc ion [1]. Genetically five different types of CAs enzymes are known till date. The ¦Á-CAs are present in vertebrates, protozoa, algae, and some bacteria and also in cytoplasm of green plants [2]. While the ¦Â-CAs are predominantly found in bacteria, algae, chloroplasts of both mono- and dicotyledons and some fungi and archaea [3], the ¦Ã-CAs are found in archaea and some bacteria [4]. Both the ¦Ä-and ¦Æ-CAs forms are present only in marine diatoms [5]. These enzymes which catalyze the interconversion between carbon dioxide and bicarbonate, with release of a proton, are involved not only in pH homeostasis and regulation but also in biosynthetic reactions, such as gluconeogenesis and ureagenesis in animals, CO2 fixation (in plants and
%U http://www.hindawi.com/journals/isrn.medicinal.chemistry/2013/107840/