The Synthesis, Antimicrobial Activity, and Molecular Docking of New 1, 2, 4-Triazole, 1, 2, 4-Triazepine, Quinoline, and Pyrimidine Scaffolds Condensed to Naturally Occurring Furochromones

This study aims to synthesize a new series of furochromone derivatives, evaluate their antimicrobial properties, and improve the permeability of potent compounds to inhibit different types of bacteria and fungi. Hence, Substituted furo[3,2-g]chromene-6-carbonitrile (3a,b) readily form 7-amino-5-methyl-furo [3,2-g]chromene-6-carbonitrile (4a,b) via reduction using sodium borohydride in methanol. The same compounds of (4a,b) were used as starting materials for the synthesis of new furochromone derivatives such as furochromeno [2,3-d]pyrimidines, N- (6-cyano- 5-methyl-furochromene) acetamide, N-(6-cyano-5-methyl-furo chromene)-2-phenyl acetamide, N- (6-cyano-5-methyl-furochromene) formimidate, furochromeno[1,2,4]triazepin-5-amine, furochrom ene-6-carboxamide, furochromeno[1,2,4]triazolopyrimidines, and furochromeno[2,3-b]quinolin- 6-amine. The structures of the new compounds were determined using spectroscopy: Nuclear Magnetic Resonance (1H, 13C), Mass spectra, Infrared, and elemental analysis. Molecular docking studies were conducted to investigate the binding patterns of the prepared compounds against DNA-gyrase (PDB 1HNJ). The results displayed that compounds furochromenotriazolopyrimidine (20a,b), furochromenoquinolin-6-amine (21a,b), furochromenotriazepin-amine (9a,b), and furo- chromenopyrimidine-amine (19a,b) were excellent antimicrobials.

[1]  M. Zaki,et al.  Synthesis and Evaluation of Some New 4H-Pyran Derivatives as Antioxidant, Antibacterial and Anti-HCT-116 Cells of CRC, with Molecular Docking, Antiproliferative, Apoptotic and ADME Investigations , 2022, Pharmaceuticals.

[2]  Abu-Hashem, AA.  Synthesis and Antimicrobial Activity of Novel 1, 2, 4-Triazolopyrimidofuroquinazolinones from Natural Furochromones (Visnagenone and Khellinone) , 2021, Medicinal Chemistry.

[3]  G. Donadio,et al.  Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids , 2021, Pharmaceutics.

[4]  Rizk E. Khidre,et al.  Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents , 2021, Scientific Reports.

[5]  Tamer M. Ibrahim,et al.  Synthesis and antimicrobial activity of some novel 1,2-dihydro-[1,2,4]triazolo[1,5-a]pyrimidines bearing amino acid moiety , 2021, RSC advances.

[6]  Mohamed S. Nafie,et al.  Synthesis, 3D-QSAR, and Molecular Modeling Studies of Triazole Bearing Compounds as a Promising Scaffold for Cyclooxygenase-2 Inhibition , 2020, Pharmaceuticals.

[7]  A. Abu‐Hashem.  Synthesis and antimicrobial activity of new 1,2,4‐triazole, 1,3,4‐oxadiazole, 1,3,4‐thiadiazole, thiopyrane, thiazolidinone, and azepine derivatives , 2020 .

[8]  M. Ibrahim,et al.  Synthesis and antimicrobial evaluation of the novel heteroannulated furo[3′,2′:6,7]chromeno[2,3‐b]pyridines: Part 1 , 2020 .

[9]  Nadia Ali Ahmed Elkanzi,et al.  Design, Synthesis, and Antimicrobial Evaluation of New Annelated Pyrimido[2,1-c][1,2,4]triazolo[3,4-f][1,2,4]triazines , 2020, Molecules.

[10]  Noha Khalil,et al.  Ammi Visnaga L., a Potential Medicinal Plant: A Review , 2020, Molecules.

[11]  M. Zaki,et al.  Synthesis of Novel Benzodifuranyl; 1,3,5-Triazines; 1,3,5-Oxadiazepines; and Thiazolopyrimidines Derived from Visnaginone and Khellinone as Anti-Inflammatory and Analgesic Agents , 2020, Molecules.

[12]  Riham F. George,et al.  Synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives: Antimicrobial activity, DNA Gyrase inhibition and molecular docking. , 2019, Bioorganic chemistry.

[13]  M. Zolfaghari,et al.  Synthesis and antimicrobial study of 1,4-dihydropyrano[2,3-c]pyrazole derivatives in the presence of amino-functionalized silica-coated cobalt oxide nanostructures as catalyst , 2019, Polyhedron.

[14]  Fatma M. Saleh,et al.  Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives. , 2019, Mini reviews in medicinal chemistry.

[15]  A. Abu‐Hashem.  Synthesis of New Furothiazolo Pyrimido Quinazolinones from Visnagenone or Khellinone and Antimicrobial Activity , 2018, Molecules.

[16]  B. Narasimhan,et al.  Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives , 2017, Chemistry Central Journal.

[17]  M. El‐Shazly,et al.  Synthesis of new quinoxaline, pyrimidine, and pyrazole furochromone derivatives as cytotoxic agents , 2017, Monatshefte für Chemie - Chemical Monthly.

[18]  T. El‐Emary,et al.  Synthesis and evaluation of chromene-based compounds containing pyrazole moiety as antimicrobial agents , 2017 .

[19]  A. Ghoneim,et al.  Synthesis and biological activities of some fused pyran derivatives , 2016 .

[20]  M. Balouiri,et al.  Methods for in vitro evaluating antimicrobial activity: A review☆ , 2015, Journal of pharmaceutical analysis.

[21]  G. Cordell,et al.  Implication of coumarins towards central nervous system disorders. , 2016, Pharmacological research.

[22]  J. Nanubolu,et al.  One-pot catalyst free synthesis of novel kojic acid tagged 2-aryl/alkyl substituted-4H-chromenes and evaluation of their antimicrobial and anti-biofilm activities. , 2015, Bioorganic & medicinal chemistry letters.

[23]  M. El‐Shazly,et al.  Synthesis, reactions and biological activities of furochromones: a review. , 2015, European journal of medicinal chemistry.

[24]  A. Shafiee,et al.  New tetracyclic tacrine analogs containing pyrano[2,3-c]pyrazole: efficient synthesis, biological assessment and docking simulation study. , 2015, European journal of medicinal chemistry.

[25]  A. Beltagy.  Chemical composition of Ammi visnaga L. and New Cytotoxic Activity of its Constituents Khellin and Visnagin , 2015 .

[26]  Amira A. Ghoneim and Ahmed F. El-Farargy.  Synthesis of Some New Chromeno[2,3-b]pyridine and [1,2,4]Triazolo[1,5- a]quinoline Nucleoside Analogues with Expected Biological Activity , 2015 .

[27]  G. N. Babu,et al.  DABCO promoted one-pot synthesis of dihydropyrano(c)chromene and pyrano[2,3-d]pyrimidine derivatives and their biological activities , 2014 .

[28]  A. Bhagavathula,et al.  Ammi Visnaga in treatment of urolithiasis and hypertriglyceridemia , 2014, Pharmacognosy research.

[29]  A. Madadkar-Sobhani,et al.  QSAR and docking analysis of A2B adenosine receptor antagonists based on non-xanthine scaffold , 2014, Medicinal Chemistry Research.

[30]  M. Vijjulatha,et al.  Synthesis, docking and evaluation of antioxidant and antimicrobial activities of novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-6-yl)selenopheno[2,3-d]pyrimidines. , 2014, European journal of medicinal chemistry.

[31]  Kui Cheng,et al.  Design, synthesis and antibacterial activity studies of thiazole derivatives as potent ecKAS III inhibitors. , 2013, Bioorganic & medicinal chemistry letters.

[32]  M. Leopoldo,et al.  A Benzopyrane Derivative as a P‐Glycoprotein Stimulator: A Potential Agent to Decrease β‐Amyloid Accumulation in Alzheimer’s Disease , 2012, ChemMedChem.

[33]  S. Muthusubramanian,et al.  Efficient Atom Economical One‐Pot Multicomponent Synthesis of Densely Functionalized 4H‐Chromene Derivatives. , 2011 .

[34]  Rizk E. Khidre,et al.  Synthesis and anti-microbial activity of some 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile derivatives. , 2011, European journal of medicinal chemistry.

[35]  A. Abu‐Hashem,et al.  Synthetic utility of bifunctional thiophene derivatives and antimicrobial evaluation of the newly synthesized agents , 2011 .

[36]  A. Abu‐Hashem,et al.  Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity , 2011, Molecules.

[37]  A. M. Vijesh,et al.  Novel Chromeno[2,3-b]-pyrimidine Derivatives as Potential Antimicrobial Agents. , 2010 .

[38]  V. Butterweck,et al.  An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. , 2010, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[39]  T. Sivakumar,et al.  Synthesis, antimicrobial and anti-inflammatory activity of some 5-substituted-3-pyridine-1, 2, 4-triazoles. , 2010 .

[40]  S. Kapur,et al.  A facile one-pot green synthesis and antibacterial activity of 2-amino-4H-pyrans and 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes. , 2009, European journal of medicinal chemistry.

[41]  Z. Kaplancıklı,et al.  New triazole and triazolothiadiazine derivatives as possible antimicrobial agents. , 2008, European journal of medicinal chemistry.

[42]  A. A. El-kateb,et al.  Simplified Approach to the Uncatalyzed Knoevenagel Condensation and Michael Addition Reactions in Water using Microwave Irradiation , 2007 .

[43]  L. Chekir‐Ghedira,et al.  Synthesis and antigenotoxic activity of some naphtho[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives. , 2007, European journal of medicinal chemistry.

[44]  P. Metz,et al.  Synthesis and molluscicidal activity of new chromene and pyrano[2,3-c]pyrazole derivatives. , 2006, Archiv der Pharmazie.

[45]  A. Kinghorn,et al.  Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy. , 2006, Anti-cancer agents in medicinal chemistry.

[46]  René Thomsen,et al.  MolDock: a new technique for high-accuracy molecular docking. , 2006, Journal of medicinal chemistry.

[47]  C. Brullo,et al.  Synthesis, antiplatelet and antithrombotic activities of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones. , 2006, Bioorganic & medicinal chemistry.

[48]  P. Metz,et al.  Synthesis and Molluscicidal Activity of 5‐oxo‐5,6,7,8‐Tetrahydro‐4H‐Chromene Derivatives , 2004, Archiv der Pharmazie.

[49]  F. Badria,et al.  SYNTHESIS OF BENZO[1,2-b: 5,4-b′]- DIFURANYL-TRIAZOLES, -OXADIAZOLES, -THIAZOLIDINONES, -THIADIAZOLES, AND THE USE OF DNA IN EVALUATION OF THEIR BIOLOGICAL ACTIVITY , 2004 .

[50]  C. Brullo,et al.  Synthesis and pharmacological evaluation of 5H-[1]benzopyrano[4,3-d]pyrimidines effective as antiplatelet/analgesic agents. , 2004, Bioorganic & medicinal chemistry.

[51]  B. Kim,et al.  Naringenin derivatives as anti-atherogenic agents. , 2003, Bioorganic & medicinal chemistry letters.

[52]  C. Brullo,et al.  Progress in 5H[1]benzopyrano[4,3-d]pyrimidin-5-amine series: 2-methoxy derivatives effective as antiplatelet agents with analgesic activity. , 2002, Farmaco.

[53]  P. Tsvetkov,et al.  DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose. , 2002, Biochemistry.

[54]  M. Head,et al.  Refined structures of beta-ketoacyl-acyl carrier protein synthase III. , 2001, Journal of molecular biology.

[55]  R. Heath,et al.  The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli. , 2000, Structure.

[56]  J. Hudson,et al.  PHYTOMEDICINES AS ANTIVIRALS , 1999 .

[57]  P. Zahradník,et al.  Infrared spectra and theoretical study of methyl, formyl and acetyl derivatives of chromones , 1993 .

[58]  H. Reichenbach,et al.  Antibiotika aus Gleitenden Bakterien, XXIII. Stigmatellin A und B — zwei neue Antibiotika aus Stigmatella aurantiaca (Myxobacterales) , 1984 .

[59]  V. Sundaramurthy,et al.  Synthesis of Coumarins with 3:4-Fused Ring Systems and their Physiological Activity , 1982 .

[60]  T. B. Lee,et al.  Benzodipyran derivatives with antiallergic activity. , 1976, Journal of medicinal chemistry.

[61]  K. Hashimoto,et al.  Quantitative and comparative studies of pharmacological features in the coronary, femoral and renal circulations with different coronary vasodilators. , 1974, Japanese journal of pharmacology.

[62]  F. Bourillet,et al.  [Spasmolytic and coronary dilator activities of some derivatives 3-ethyl chromone]. , 1962, Therapie.

[63]  N. Metropolis,et al.  Equation of State Calculations by Fast Computing Machines , 1953, Resonance.