An Andrographolide from Helichrysum caespitium (DC.) Sond. Ex Harv., (Asteraceae) and Its Antimicrobial, Antiquorum Sensing, and Antibiofilm Potentials

SIMPLE SUMMARY: Gonorrhea is a major public health concern globally and more than 800,000 new infections occur in the USA alone each year, according to the Centers for Disease Control (CDC). Health complications triggered by gonorrheal infection include HIV/AIDS and infertility, just to mention but a few. The Gram-negative gonococci bacteria resist known antibiotic treatments over the years, including penicillin, tetracycline, and fluoroquinolones, with only cephalosporins available for treatment currently. Resistance to the cephalosporins in many countries underlines the dire need for new antigonorrheal drugs. This study explored the potential of isolating an antigonorrheal compound from a nonpolar extract of Helichrysum caespititium. The 10-methyl-8-(propan-17-ylidene)naphthalen-9-yl)-11-vinyl-14-hydroxyfuran-16-one (CF6) isolated from the chloroform extract of the plant inhibited Neisseria gonorrhoeae with a MIC value of 60 µg/mL compared to ciprofloxacin with a MIC of 1 µg/mL. This compound indicates potential as a new antigonorrheal lead molecule. ABSTRACT: Helichrysum caespititium (DC.) Sond. Ex Harv., (Asteraceae) is a medicinal plant indigenous to South Africa. Its non-polar extracts exhibit significant antimicrobial and, in particular, antigonorrheal activity. This study aimed at isolating and purifying the active antigonorrheal compound from its chloroform extract and validating its inhibition potential on quorum sensing (QS) and biofilm formation of multi-drug resistant (MDR) pathogens. Phytochemical investigation of aerial parts of H. caespititium afforded a diterpene lactone (CF6). The effect of CF6 on violacein production and biofilm formation was studied using in vitro quantitative violacein inhibition (Chromobacterium violaceum) and biofilm formation (Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, and Pseudomonas aeruginosa). The structure of CF6 was characterized using FTIR, NMR, and UPLC-MS data accordingly, as 10-methyl-8-(propan-17-ylidene)naphthalen-9-yl)-11-vinyl-14-hydroxyfuran-16-one. The susceptibility testing of the pathogens against CF6 revealed Neisseria gonorrhoeae was noticeably susceptible with a MIC value of 60 µg/mL, while Streptococcus pyogenes and Staphylococcus aureus showed MIC of 125 µg/mL. All gram-negative pathogens, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa were inhibited at 250 µg/mL. CF6 also inhibited the production of violacein by 51.88% at 250 µg/mL and prevented cell attachment by 40.76–81.18%, with N. gonorrhoeae being highly prohibited from forming biofilm. In conclusion, 10-methyl-8-(propan-17-ylidene)naphthalen-9-yl)-11-vinyl-14-hydroxyfuran-16-one is the first of its kind to be isolated from the non-polar (chloroform) extract of South African Helichrysum caespititium with antigonorrheal, antimicrobial, antiquorum sensing, and antibiofilm properties. The compound may serve as a drug candidate against MDR pathogens.