title: Novel amalgamation of phthalazine-quinolines as biofilm inhibitors: One-pot synthesis, biological evaluation and in silico ADME prediction with favorable metabolic fate.
abstract: A facile and highly efficient one-pot synthesis of phthalazine-quinoline derivatives is reported via four component reaction of phthalic anhydride, hydrazine hydrate, 5,5-dimethyl 1,3 cyclohexanedione and various quinoline aldehydes using PrxCoFe2-xO4 (x=0.1) nanoparticles as a catalyst. The synthesized compounds have been evaluated for anti-biofilm activity against Pseudomonas aeruginosa and Candida albicans. The compounds 12a (IC50=30.0μM) and 12f (IC50=34.5μM) had shown promising anti-biofilm activity against P. aeruginosa and C. albicans, respectively, when compared with standards without affecting the growth of cells (and thus behave as anti-quorum sensing agents). Compounds 12a (MIC=45.0μg/mL) and 12f (MIC=57.5μg/mL) showed significant potent antimicrobial activity against P. aeruginosa and C. albicans, respectively. Thus, the active derivatives were not only potent biofilm inhibitors but also efficient antimicrobial agents. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antimicrobial drug discovery initiatives.
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, M.S., India. Electronic address: zahidzresearch@gmail.com.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Zaheer
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, M.S., India.
authors.forename: Firoz A Kalam
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, M.S., India.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
authors.affiliation: Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, M.S., India.
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Materials Research Laboratory, Srikrishna Mahavidyalaya Gunjoti, Omerga, Osmanabad 413 613, M.S., India.
authors.forename: K S
authors.initials: KS
authors.lastname: Lohar
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D002177:Candidiasis / Q000188:drug therapy; D003198:Computer Simulation; D006801:Humans; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D010793:Phthalazines; D011804:Quinolines
keywords: Antibacterial activity; Antifungal activity; Biofilm inhibition; In silico studies; Phthalazine–quinolines; Pr(x)CoFe(2−)(x)O(4) (x=0.1) nanoparticles