Design and Synthesis of Novel Benzopyran‐2‐one Derivatives of Expected Antimicrobial Activity through DNA Gyrase‐B Inhibition

Abstract

In an attempt to find a new class of antibacterial agents, we have synthesized thirty new coumarin (2H-benzopyran-2-one) analogues. These derivatives include substituted azetidin-2-ones (beta-lactam) 3a-f, pyrrolidin-2-ones 4a-f, 2H-1,3,4-oxadiazoles 5a-f, and thiazolidin-4-ones 6a-f attached to 4-phenyl-2H-benzopyran-2-one through an oxyacetamido or an oxymethyl bridge. The target compounds were synthesized starting from 2-oxo-4-phenyl-2H-benzo[b]pyran-7-yl-oxyacetic acid hydrazides 2a-f. The new compounds were evaluated as DNA gyrase-B inhibitors through molecular modeling and docking techniques using the Molsoft ICM 3.4-8C program. The synthesized compounds were also screened for antibacterial activity against four different species of Gram-positive and Gram-negative bacteria; as well as screening against C. albicans for antifungal activity. The molecular modeling data were in accordance with the antimicrobial screening results.

In front of and behind the replication fork: bacterial type IIA topoisomerases

“…Novel inhibitors thus far tested include indolinones, catechins, azoles, benzopyranones, imidazolo-and triazolo-pyridines, benzimidazoles and chiral barbituric acid derivatives [163][164][165][166][167][168][169][170]. Among these compounds, members of the latter two families were endowed with the ability to inhibit both GyrB and ParE ATPases, hence behaving as especially valuable dual inhibitors.…”

Design and Synthesis of Peptide Derivatives Act as DNA Binding Agent and Discovery of Potent Carbonic Anhydrase Inhibitors Using Docking Studies

“…All the products (6-8) were chromatographically homogeneous by iodine and benzidine development. (9)(10)(11)(12)(13)(14) General procedures To a solution of amino acid methyl ester hydrochloride (1.5 equiv) was dissolved in THF, triethylamine (2 ml) was added, the solution was stirred at 20°C for 30 min and cooled to O°C, dipeptide (3-5;1equiv) in THF (50 ml) and DCC (1 equiv) were added to the above mixture. The reaction mixture was stirred for 6 hr at 0°C and for another 12 hr at room temperature.…”

“…The structural changes of DNA based on the interaction of small molecular weight ligands with DNA have attracted attention in the medicinal design of anticancer and anti-AIDS drugs (6,7) . Some chromen-2-one (coumarine) derivatives have been reported to possess anti-SARS agent (8) , antioxidant properties (9) , anti-fungal (10) , anti-bacterial (11) , antiinflammatory (12) , antitumor (13) , inhibitors of pancreatic cholesterol (14) , estrogen receptor (15) and treatment of Alzheimer diseases (16) . In addition, many drugs consist of amino acid moieties as; AG7088 (which was developed by Pfizer and used for the treatment of rhinovirus, which can cause the common cold), which contain phenylalanine moiety (17) .…”

An Insight into the Anticancer Activities of Ru(II)-Based Metallocompounds Using Docking Methods

“…Other receptors considered in these work besides DNA are thioredoxin reductase (TrxR) [14], histone protein in a nucleosome core particle (HP-NCP) [15], BRAF Kinase [16], recombinant human albumin (rHA) [17,18], thymidylate synthase (TS) [19], ribonucleotide reductase (RNR) [20], histone deacetylase (HDAC7) [20], cathepsin B (CatB) [14], topoisomerase II (TopII) [21,22] and DNA gyrase. All these have been reported to play significant roles in cancer growth and metastasis, except DNA gyrase, which is a notable bacterial enzyme [23,24], considered in this project for the purpose of seeing if some of these metallocompounds can play a dual role.…”