Synthesis and Biological Evaluation of Tricyclic Guanidine Analogues of Batzelladine K for Antimalarial, Antileishmanial, Antibacterial, Antifungal, and Anti‐HIV Activities. (28th March 2013)

• Record Type: Journal Article
• Authors: Ahmed, Nafees; Brahmbhatt, Keyur G.; Khan, Shabana I.; Jacob, Melissa; Tekwani, Babu L.; Sabde, Sudeep; Mitra, Debashis; Singh, Inder P.; Khan, Ikhlas A.; Bhutani, Kamlesh K.
• Is Part Of: Chemical biology & drug design. Volume 81:Number 4(2013:Apr.)
• Page Start: 491
• Page End: 498
• Publication Date: 2013-03-28
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.1427
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Fifty analogues of batzelladine K were synthesized and evaluated for <italic>in vitro</italic> antimalarial (<italic>Plasmodium falciparum</italic>), antileishmanial (<italic>Leishmania donovani</italic>), antimicrobial (panel of bacteria and fungi), antiviral (HIV‐1) activities. Analogues <bold>14h</bold> and <bold>20l</bold> exhibited potential antimalarial activity against chloroquine‐sensitive D6 strain with IC₅₀ 1.25 and 0.88 μ<sc>m</sc> and chloroquine‐resistant W2 strain with IC₅₀ 1.64 and 1.07 μ<sc>m</sc>, respectively. Analogues <bold>12c</bold> and <bold>14c</bold> having nonyl substitution showed the most potent antileishmanial activity with IC₅₀ 2.39 and 2.78 μ<sc>m</sc> and IC₉₀ 11.27 and 12.76 μ<sc>m</sc>, respectively. Three analogues <bold>12c</bold>, <bold> 14c, </bold> and <bold>14i</bold> were the most active against various pathogenic bacteria and fungi with IC₅₀ &lt; 3.02 μ<sc>m</sc> and MIC/MBC/MFC &lt;6 μ<sc>m</sc>. Analogue <bold>20l</bold> having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV‐1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.</p> </abstract>