Development of Repetitive Synergism in Calitropis procera Extract with Ampicillin for Combating Drug Resistance in Clinical Bacteria and Identification of its Bioactive Components using GS-MS Analysis.

The pursuit of innovative approaches to develop lead compounds that exhibit selectivity, efficacy, and safety as potential candidates for clinical trials poses a significant scientific challenge. Natural products, with their inherent diversity, offer unique pharmacophores, chemotypes, and scaffolds that can be harnessed to create effective drugs targeting various infections and diseases. This study introduces a straightforward, rudimentary, and environmentally sustainable method to enhance the antimicrobial activity of two less potent antimicrobial agents, fostering consistent and repetitive synergism against drug-resistant clinical bacteria. The aqueous extract of fresh leaves and flowers of Calotropis procera was subjected to a reaction with a 1 mg/mL ampicillin solution under heat and acidic conditions. The resultant sample exhibited pronounced synergy and heightened susceptibility against resistant strains of Staphylococcus aureus and Salmonella spp, augmenting their zones of inhibition from 0 mm to 16.8 mm and from 5.3 mm to 21.4 mm, respectively. Utilizing gas chromatography-mass spectrometry (GC-MS) analysis, the study identified 53 phytochemicals in the extract, with oleic acid (13.04%), 1,1,1,3,5,5,7,7,7-nonamethyl-3-(trimethylsiloxy) tetrasiloxane (9.50%), 9-heptadecanone (3.75%), cystamine (3.35%), and tetrahydro-4H-pyran-4-ol (3.15%) emerging as the top five most abundant phytochemicals. Notably, 18 out of the 53 phytochemicals were associated with known biological activities. Some underwent molecular transformations, generating new molecules or analogues of existing biologically active compounds under the reaction conditions applied. The analysis revealed the discovery of compounds such as farnesol, cystamine, cystine, metaraminol, dl-phenylephrine, and two distinct substituted amphetamine compounds. Three phytochemicals demonstrated anticancer properties, namely farnesol, 4-amino-1-pentanol, and an imidazole derivative resembling the drug Ribavir. The study's findings underscore the potential of medicinal plant phytochemicals in synthetic combination reactions, either with themselves or other drugs/reagents, to yield a diverse array of compounds exhibiting significant pharmacological activities. These compounds may serve as valuable starting materials, intermediates, or derivatives in pharmaceutical production.