Inhibition of bacterial RNA polymerase by the cyanobacterial metabolites 12-epi-hapalindole E isonitrile and calothrixin A

Abstract

The alkaloid 12-epi-hapalindole E isonitrile, from a cyanobacterial Fischerella species, and the indolophenanthridine calothrixin A, from Calothrix, inhibited Escherichia coli RNA polymerase competitively with respect to ATP, and non-competitively with respect to UTP. The inhibition was dependent on the order of addition of the inhibitors. The K I values, with ATP as the variable substrate, were 1.3 þ 0.2 mM and 0.23 þ 0.11 mM, respectively. Based on comparisons with the sensitivity of whole cells to these inhibitors, it is concluded that other targets in addition to RNA polymerase may also be implicated in their action. ß

Hapalindole-related alkaloids from the cultured cyanobacterium Fischerella ambigua

“…Several recent reviews have discussed their potential as a source of pharmaceutical leads (Sielaff et al , 2006; Tan, 2007; Williams, 2009). One family of compounds that has been explored for their pharmaceutical potential are isonitrile containing indole alkaloids, such as hapalindoles (Doan et al , 2001; Huber et al , 1998; Klein et al , 1995; Moore et al , 1987; Moore et al , 1989), ambiguine isonitriles (Huber et al , 1998; Raveh and Carmeli, 2007; Smitka et al , 1992), fischerindoles (Park et al , 1992) and wetwitindolinones (Jimenez et al , 1999; Stratmann et al , 1994) from branched filamentous cyanobacteria of the genera Fischerella , Hapalosiphon , Westiella , and Westiellopsis . Since the first report of hapalindoles in 1984 by Moore and coworkers (Moore et al , 1984), over 60 natural products belonging to this family have been identified (Richter et al , 2008).…”

Assessment of the antibacterial activity of macroalgae Cladophora crispata extract against extended spectrum beta-lactamase producing Escherichia coli isolated from diarrheic children

“…The antibacterial activity of algal alkaloids may be attributed to their ability for inhibition of RNA polymerase of E. coli result in inhibited both RNA and protein synthesis ( Doan et al, 2001), alkaloid also inhibit DNA synthesis by inhibition of the topoisomerase enzyme that control the DNA replication of E. coli leading to morphological changes and cell lysis ( Karou et al, 2005).…”

Total Synthesis of Calothrixin B via an Intramolecular Baylis‐Hillman Cyclization/6π Electrocyclization/Dehydro‐aromatization Sequence and a Specific Oxidative Quinone Formation

“…Calothrixin A is known to be a N ‐oxide analog of calothrixin B. Calothrixins exhibit excellent antimalarial activity including inhibitory effects on a chloroquine resistant strain of the malarial parasite Plasmodium falciparum . They show antiproliferative properties against several cancer cell lines as well as human DNA topoisomerase I poisoning activity [2] and also act as inhibitors of bacterial‐RNA polymerase [3] . In addition, calothrixin A is also known to induce the intracellular formation of reactive oxygen species [4] .…”