PHYTOTHERAPY RESEARCH Phytother. Res. 17, 434 – 436 (2003) Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ptr.1284 Copyright © 2003 John Wiley & Sons, Ltd. Received 31 October 2002 Accepted 18 November 2002 John Wiley & Sons, Ltd. SHORT COMMUNICATION SHORT COMMUNICATION Cryptolepine Hydrochloride: A Potent Antimycobacterial Alkaloid Derived from Cryptolepis sanguinolenta Cryptolepine Hydrochloride Simon Gibbons 1 *, Fatemeh Fallah 2 † and Colin W. Wright 2 1 Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK 2 School of Pharmacy, University of Bradford, West Yorkshire BD7 1DP, UK The activity of cryptolepine hydrochloride, a salt of the main indoloquinoline alkaloid from the West African medicinal plant Cryptolepis sanguinolenta, was assessed against the fast growing mycobacterial species Mycobacterium fortuitum, which has recently been shown to be of use in the evaluation of anti- tubercular drugs. The low minimum inhibitory concentration (MIC) of this compound (16 μg/mL) prompted further evaluation against other fast growing mycobacteria namely, M. phlei, M. aurum, M. smegmatis, M. bovis BCG and M. abcessus and the MICs ranged over 2–32 μg/mL for these species. The strong activity of this agent, the need for new antibiotics with activity against Mycobacterium tuberculosis, coupled with the ethnobotanical use of C. sanguinolenta extracts to treat infections, highlight the potential of the cryptolepine template for development of antimycobacterial agents. Copyright © 2003 John Wiley & Sons, Ltd. Keywords: Mycobacterium; antibacterial; cryptolepine; Cryptolepis sanguinolenta. INTRODUCTION There is still much opportunity to exploit the ethno- pharmacological route to new drug leads (Heinrich and Gibbons, 2001), particularly in the discovery of antibiotic lead compounds, where there is a pressing need for new classes of antimycobacterial agents to manage infections caused by fast growing species. Addi- tionally there is a requirement for new antibiotics to treat tuberculosis (TB) where multidrug-resistant (MDR) strains of Mycobacterium tuberculosis are implicated. Treatment of TB is protracted, and comprises a sche- dule of antimycobacterial drugs of which rifampicin, isoniazid, pyrazinamide and ethambutol are the core. Unfortunately, resistance to these agents is becoming increasingly common due to the emergence of strains which possess MDR mechanisms (Raviglione et al., 2001). Plants are an excellent source of antimycobacterial compounds (Newton et al., 2000; Cantrell et al., 2001; Newton et al., 2002) but until recently there has been little pressure to develop natural products from plants as antitubercular leads, due to the susceptibility of strains to standard agents. In a project to discover antimycobacterial plant derived natural products, cryptolepine hydrochloride (1) was screened in an in vitro assay using Mycobacterium fortuitum (ATCC 6841). This has recently been shown to be of use as an alternative screening model to M. tuberculosis for potential antitubercular drugs (Gillespie et al., 2001), can be handled in a class II microbiolo- gical laboratory and is a fast growing strain with the assay being complete in 72 h. The current study with cryptolepine was driven because of the large number of ethnopharmacological uses for the producing species of the parent alkaloid, Cryptolepis sanguinolenta, which in West Africa is widely used particularly for the treatment of microbial infections and malaria (Silva et al., 1996; Tona et al., 1999). Previous work on the antibacterial properties of this alkaloid have focused on diarrhoeal bacteria (Paulo et al., 1994), Escherichia coli and yeasts (Sawyer et al., 1995; 1997), antistaphylococcal activity (Boakye-Yiadom and Heman-Ackah, 1979), and one report on the activity of the free base and the hydrochloride against Mycobac- terium fortuitum (Cimanga et al., 1996) although there is no further evaluation of this compound against other species of mycobacteria. Cryptolepine has also recently been shown to intercalate into DNA at * Correspondence to: Dr S. Gibbons, Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK. E-mail: simon.gibbons@ulsop.ac.uk † Present address: Department of Microbiology, Shaheed Beheshti University of Medical Sciences and Health Sciences, Tehran, Iran.