title: Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction.
abstract: In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho(3+) doped CoFe2O4 nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50 value=95.50, 95.00 and 99.00μg/mL, respectively) when compared to the standard sodium stibogluconate (IC50=490.00 μg/mL). The compounds 13a (IC50=12.40 μg/mL), 13d (IC50=13.49 μg/mL), 13g (IC50=13.24 μg/mL) and 13l (IC50=13.74 μg/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50=16.5 μg/mL) and ascorbic acid (IC50=12.8 μg/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent.
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, (M.S.), India. Electronic address: jnsangshetti@rediffmail.com.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, (M.S.), India.
authors.forename: Firoz A
authors.initials: FA
authors.lastname: Kalam Khan
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, (M.S.), India.
authors.forename: Abhishek A
authors.initials: AA
authors.lastname: Kulkarni
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: Department of Chemistry, Jawahar Art Science and Commerce College, Andur, Osmanabad 413603, (M.S.), India.
authors.forename: Amol M
authors.initials: AM
authors.lastname: Pachpinde
authors.affiliation: Materials Research Laboratory, Srikrishna Mahavidyalaya Gunjoti, Omerga, Osmanabad 413 613, (M.S.), India.
authors.forename: Kishan S
authors.initials: KS
authors.lastname: Lohar
authors.affiliation: Shivaji University, Vidyanagar, Kolhapur 416 004, (M.S.), India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology; D062105:Molecular Docking Simulation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D000981:Antiprotozoal Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; C030123:coumarin; D010088:Oxidoreductases; C085592:pteridine reductase
keywords: Antileishmanial; Antioxidant; Ho(3+) doped CoFe(2)O(4) nanoparticles; Indolyl–coumarin hybrids; Molecular docking studies