Title : Chemistry of phyto-chemicals from cassia fistula, suregada multiflora, and jatropha gossipifolia and advancement for the drug discovery against multi-drug resistant bacteria
Abstract:
Escherichia coli, Salmonella enterica, Acinetobacter baumannii, Pseudomonas aeguginosa, Enterococcus faecium, and Klebsiella pneumonia-mediated infections were not cured by antibiotics due to multiple large and small MDR plasmids containing >10 MDR (bla, cat, strA/B, aac, aph, aad) genes and drug efflux genes (tetC, acrAB-TolC, mexAB-OprM). Thus, the development of new antibacterial drugs is urgently needed. We have found a new abundant terpentine-polybromophenol phyto-chemical from Cassia fistula bark that inhibits MDR bacteria isolated from Ganga River water, human and animal, targeting RNA Polymerase enzyme. On TLC, a grey colour major band ran fast (CU1=6.6% of bark and ~30% of crude ethanol extract of bark) which purified on HPLC C18 column at 3 min. The CHN Elements analysis showed low carbon content (35.9%) and no nitrogen suggesting a polyphenol or glycoside with halogen-substituent. CU1 Mass is 897 Daltons with fragments of 515, 325, 269, 180 Daltons and six bromine substitutions confirmed by 82 molecular mass of DBr deviate six larger fragments. The FT-IR confirmed a broad band at 3500-3000 cm-1 for –OH whereas two strong peaks at 1552cm-1 for aromatic C=C and 1408cm-1 for phenol. Proton-NMR concluded polymeric phenol at δ 4.86-4.91 ppm and titrated at δ 3.57-3.618 ppm with phenolic Bromo-substituents. Carbon-NMR identified a strong peak at δ=23.7ppm for many C-Br and at 165ppm for a polybenzoid compound. The CU1 inhibited the RNA Polymerase of E. coli and M. tuberculosis but not DNA polymerase. Gel shift assays demonstrated that the CU1 drug interacted with the enzyme and inhibited its binding to open promoter complex. CU1 did not inhibit moly fishes and rats at low concentrations. Thus, CU1 phytochemical may be an alternative safer and lower-cost drug against MDR-TB and other MDR pathogens as well as for the treatment of corona-virus patients with MDR co-infections. The NU2 phytochemical was a glycoside and inhibited the DNA topoisomerase of Escherichia coli. The Jatropha gossipifolia root, Shorea robusta inner root, and Trapa bispinota fruit peel ethanol extract also have antibacterial activities. MDR-bacteria were isolated from Ganga River water, rainwater, chicken meat, milk and human hair and at least resistant to three antibiotics comprising ampicillin, tetracycline, chloramphenicol, streptomycin, erythromycin and ciprofloxacin. We think antibiotic void will increase due to a few reasons: (1) MDR genes are accumulated in large conjugative plasmids with many IS elements; (2) the spread of MDR genes in bacteria is increasing at ~5%/year and (3) mdr genes protect gut microbiota from antibiotics. Thus, CU1, NU2, JU2 phytochemicals should be used to curve MDR bacterial infections.
