Synthesis and Antibacterial Evaluation of Novel Heterocyclic Compounds Containing a Sulfonamido Moiety

Aiming for the synthesis of new heterocyclic compounds containing a sulfonamido moiety suitable for use as antibacterial agents, the precursor ethyl {[4-N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenylazo}cyanoacetate was reacted with a variety of active methylene compounds producing pyran, pyridine and pyridazine derivatives. Also, the reactivity of the precursor hydrazone towards hydrazine derivatives to give pyrazole and oxazole derivatives was studied. On the other hand, treatment of the same precursor with urea, thiourea and/or guanidine hydrochloride furnished pyrimidine and thiazine derivatives, respectively. The newly synthesized compounds were tested for antibacterial activity, whereby eight compounds were found to have high activities

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives

Abstract An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with − 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein

6-Iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one as building block in heterocyclic synthesis

<p>As a part of ongoing studies in the synthesis of a variety of heterocycles of biological importance, we report here an efficient and convenient method for the synthesis of novel compounds from 6-iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one <b>1</b> as building block. The reaction of benzoxazinone <b>1</b> with various reagents such as diethylmalonate, sodium azide, and phosphorus pentasulfide yielded the compounds <b>2–5</b>. The behavior of benzothiazin-4-thione <b>5</b> toward formamide and hydrazine hydrate was investigated, forming the compounds <b>6</b> and <b>7</b>. The reaction of quinazolinone derivative <b>8</b> with β-D-glucose pentaacetate, ethyl 2-methyl-5-((1S,2R,3R)-1,2,3,4-tetrahydroxybutyl)furan-3-carboxylate, epichlorohydrin and benzenesulphonyl chloride afforded quinazolinone derivatives <b>9, 10, 12,</b> and <b>13</b> respectively. The reaction of quinazolinone derivative <b>10</b> with acetic anhydride resulted in formation of the acylated compound <b>11</b>. The behavior of quinazolinylacetohydrazide derivative <b>14</b> toward carbon electrophiles^[<a href="#CIT0016" target="_blank">¹⁶</a>^] has been investigated by its reaction with ethyl benzoylacetate, potassium thiocyanate, and phenyl isothiocyanate, affording the quinazolinone derivatives <b>15, 16,</b> and <b>18</b>, respectively. Treatment of compound <b>16</b> with sodium hydroxide followed by hydrochloric acid yielded the mercapto-triazole derivative <b>17</b>. The structures of the newly synthesized compounds were confirmed by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and mass spectra. The antimicrobial activities of some of the synthesized compounds were preliminarily evaluated.</p

Regioselectivity and regiospecificity of benzoxazinone (2-isopropyl-4<i>H</i>-3,1-benzoxazinone) derivatives toward nitrogen nucleophiles and evaluation of antimicrobial activity

<p>A novel group of 6-iodoquinazolin-4(<i>3H</i>)-one derivatives was prepared. The reaction of the benzoxazinone <b>3</b> with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone <b>4</b> with hydrazonyl chloride have been shown to proceed with a high degree of regioselectivity at C(2). Spiro heterocycles have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties; thus reaction of acetohydrazides <b>10a–c</b> afforded the spiro compounds <b>11a–c</b>. The acetohydrazide derivative <b>7</b> reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds <b>12–16</b>, respectively. The structures of all the synthesized compounds were inferred by infrared, ¹H NMR, and mass spectra as well as elemental analyses. The antimicrobial activities of some of the synthesized products were preliminarily evaluated.</p