“Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine.
Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron-sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function.
In this investigation, the 2Fe-2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs-9 obtained from literature sources and 7 identified via fingerprint similarity searches.
The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics.”
https://www.mdpi.com/2079-7737/14/9/1272
“Neisseria gonorrhoeae, the bacterium responsible for gonorrhoea, has developed increasing resistance to multiple antibiotics, making new treatment strategies urgently needed. This study explores the potential of cannabinoids and their derivatives as antimicrobial agents targeting N. gonorrhoeae.
Using computational methods, including molecular docking and fingerprint-based compound searches, the study identified five promising cannabinoid compounds with strong binding affinities to the 2Fe-2S iron–sulfur cluster binding domain-containing protein, a critical bacterial enzyme involved in electron transport and cellular function. These include 1,3-Benzenediol (a cannabidiol derivative), Ferruginene C, Dronabinol, Cannabinolic acid A (CBNA), and Cannabigerolic acid (CBGA). Their interactions were visualized using PyMOL and PLIP, revealing significant hydrogen bonding and hydrophobic interactions at active binding sites. Additionally, drug-likeness and pharmacokinetic assessments were performed, showing favorable absorption and low toxicity for several compounds compared to standard antibiotics.
Importantly, these cannabinoids showed potential to disrupt bacterial metabolic processes without inducing typical resistance pathways. The findings support further exploration of Phyto cannabinoids as natural alternatives for treating multidrug-resistant N. gonorrhoeae, with the 2Fe-2S cluster protein as a novel target. Further in vivo validation is recommended to confirm their therapeutic efficacy and safety.”
