“Non-Antibiotics- an Alternative for Microbial Resistance: Scope & Hope”

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4 Nonantibiotics – An Alternative for Microbial Resistance: Scope and Hope Debprasad Chattopadhyay, Soumen Kumar Das, Arup Ranjan Patra, and Sujit K. Bhattacharya

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Abstract
The antimicrobial activity of nonchemotherapeutic compounds, such as methylene blue, phenothiazine, thioxanthene and related agents, has been known since the time of Paul Ehrlich (1854–1915). In this context the term ‘nonantibiotics’ was introduced to include a variety of compounds used in the management of pathological conditions of noninfectious etiology. Despite the availability of hundreds of anti-infective drugs the emergence of ‘antibiotic resistance’ and new infectious agents creates the therapeutic challenge to the medical community. Hence, the search for newer agents to tackle the global problem is continuing. It has been noted that many of the phenothiazines, thioxanthenes, other neurotropics, antihistamines, anesthetics, analgesics, antihypertensives, muscle relaxants, some cardiovascular agents and so on can inhibit diverse classes of microbes, as well as the drug-resistant strains at different dose levels, by modifying the architecture of the microbial membrane and its permeability. A review of the literature suggests that some of these membrane-active compounds can enhance the activity of conventional antibiotics, eliminate natural resistance to specific antibiotics (reversal of resistance) and exhibit strong activity against multidrug-resistant forms of Staphylococcus aureus, Escherichia coli, Salmonella spp., Mycobacterium tuberculosis, Plasmodium falciparum and so on. This chapter covers the antimicrobial activity of some nonantibiotics, especially against drug-resistant microbes, that cause therapeutic challenge with an emphasis on the group of drugs used as antihistamines, sedatives, hypnotics and so on, and their stereoisomers.

4.1 Introduction

Antibiotics are substances produced by microorganisms that can destroy or inhibit the growth of other microorganisms and can even act against some cancer cells. On the

New Strategies Combating Bacterial Infection. Edited by Iqbal Ahmad and Farrukh Aqil Copyright Ó 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32206-0

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j 4 Nonantibiotics – An Alternative for Microbial Resistance: Scope and Hope other hand, substances of nonmicrobial origin that have similar effects on microbes or malignant cells are described as chemotherapeutic agents [1]. Drugs that are neither antibiotics nor antimicrobial chemotherapeutic agents, but which possess antimicrobial properties, are termed ‘nonantibiotics’ [2]. Pharmacologically, drugs have been classified on the basis of their apparently major and predominant pharmacological action, such as antihistamines, analgesics, antihypertensives, neuroleptics, local anesthetics, anti-inflammatory agents and so on. Nevertheless many of the drugs are basically multifunctional and show different activity at different dose levels [3]. This multiplicity of function, other than their first described one, may be quite significant. Hence, redescriptions of such drugs are possible (e.g. Prontosil, an azo dye containing a sulfonamide group, was later developed as an antibacterial agent) [4, 5]. Similarly, the synthetic nitrofurantoin is a selective antibacterial against urinary tract bacteria, but can also damage mammalian DNA [6]. Likewise, the phenazine dye clofazamine possesses antihistaminic, anti-inflammatory as well as powerful antibacterial action against leprosy bacilli by inhibiting DNA template formation...
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