Indian Journal of Chemistry Vol. 47B, May 2008, pp. 740-747 Biologically active hydroxymoyl chlorides as antifungal agents † Tabasum Ismail a , Syed Shafi a , Parvinder Pal Singh a , Naveed Ahmed Qazi a , Sanghapal D Sawant a , Intzar Ali b , Inshad Ali Khan b , H M S Kumar* a , Ghulam Nabi Qazi d & M Sarwar Alam c a Departments of Synthetic Chemistry & b Biotechnology , c Department of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi , 110 062 d Indian Institute of Integrative Medicine (formerly RRL, Jammu), Canal Road, Jammu Tawi 180 001, India E-mail: hmskumar@yahoo.com Received 12 July 2007; accepted (revised) 19 February 2008 Several oximes and oxime ethers have been developed as antimicrobial agents. A series of chlorooximes (hydroximoyl chlorides) have been synthesized and tested for antifungal activity under in-vitro conditions against Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. The derived antifungal activity has been compared with the corresponding oximes. The results show that most of the chlorooximes exhibit potent antifungal activity with anti-isomers showing better activity. It is observed that most of the chlorooximes show interesting antifungal activity (MICs < 32 µg/mL) compared to oximes. Compound 3q (2,3-dimethoxy phenyl hydroxymoyl chloride) is the most active compound. This compound is active against all the Candida species (MIC 0.5 µg/mL) as well as filamentous fungi with MIC range of 2-4 µg/mL. This series of compounds are fungicidal in nature as evident from the MFC results. Keywords: Hydroxymoyl chloride (chlorooxime), oximes, hydroxylamine hydrochloride, N-chlorosuccinimide, antifungal activity It is well known that fungi cause many diseases of plants, animals, and humans and often acquire drug resistance during treatment. Since fungal infections are caused by eukaryotic organisms, for this reason they generally present more difficult therapeutic problems than do bacterial infections. Fungal infec- tions have emerged as a major cause of morbidity and often of mortality in immunocompromised and debilitated patients over the past two decades 1,2 . Many of the currently available drugs are toxic, produce recurrence because they are fungi static and not fungicidal or lead to the development of resistance due in part to the prolonged periods of administration of the available antifungal drugs. The usage of most antimicrobial agents is limited, not only by the rapidly developing drug resistance, but also by the unsatisfactory status of present treatments of bacterial and fungal infections and drug side-effects 3-6 . Although the use of a new generation of triazoles, the available polyenes in lipid formulations, the use of echinocandins or the combination therapy have been introduced as alternatives in the last ten years, fungal infections remain difficult to eradicate 7 . There is, therefore, a clear need for the discovery of new chemical entities with antifungal properties, which could lead to the development of new drugs for the management of fungal infections. Oximes and their derivatives have attracted considerable attention since the past few decades due to their chemotherapeutic value. Many oximes are found to be anti- hyperglycemic 8 , anti-neoplastic 9 , anti-inflammatory 10 , anti-leishmanial 11 , and VEGFR-2 kinase inhibitors 12 . Oximes also possess transcriptional activity 13 . Besides this, several oximes and oxime-ethers have been developed as anti-microbial agents 14 . The current study attempted to assess particularly the antifungal effects of various chlorooximes on different strains of fungi such as Candida albicans, C. parapsilosis, C. glabrata, C. krusei, Aspergillus fumigatus, A. flavus and A. niger to explore their therapeutic potential. Chemically, chlorooximes are important intermediates for the synthesis of nitrile oxides which in turn are used in a number of chemical reactions such as dipolar cyloaddition reactions and lead to the synthesis of a variety of heterocycles like isoxazoles, isoxazolines, etc. Even though oximes were used as ⎯⎯⎯⎯⎯⎯ † IIIM Communication No. SCL-07/18