Inhibitory activity of benzo[h]quinoline and benzo[h]chromene in human glioblastoma cells

Purpose: To carry out a neat synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenylbenzo[h]quinoline-3- carbonitrile (compound 2) and 2-amino-5,6-dihydro-8-methoxy-4-phenyl-4H-benzo[h]chromene-3- carbonitrile (compound 3) and evaluate their cytotoxic activity in human glioblastoma cells.Methods: Benzo[h]quinoline and benzo[h]chromene were synthesized by treating 6-methoxy-1- tetralone with benzylidenemalononitrile under microwave irradiation. The structures of compounds 2 and 3 were confirmed by elemental, spectral, and x-ray crystallographic analyses. The cytotoxic activity of compounds 2 and 3 was evaluated using WST-1 assay in U373 human glioblastoma cell line.Results: The molecular structures of compounds 2 and 3 were demonstrated unambiguously from single crystal x-ray measurements and they crystallized in triclinic form, P-1, for both compounds. In vitro cytotoxic activity data for compound 2 in human glioblastoma cell line (U373) indicate that no significant cytotoxicity was observed. On the other hand, compound 3 showed highly significant cytotoxic effects on U373 cells at concentrations starting from 0.1 μg/ mL.Conclusion: Compound 3 produces a decrease in cell viability with approximately 80 % cell death while compound 2 did not indicate significant cytotoxic activity. This suggests that the chromene moiety of compound 3 may be responsible for its high cytotoxicity.Keywords: Hydronaphthaline, Benzo[h]quinolone, Benzo[h]chromene, X-ray crystallography, U373 human glioblastoma, Cytotoxicity, Chromene moiet

A convenient synthesis of 5-amino-4-(2-benzothiazolyl)pyrazoles

1175-117

Synthesis and greener pastures biological study of bis-thiadiazoles as potential Covid-19 drug candidates

A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2′-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins M$^{pro}$ and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with M$^{pro}$ was (−9.2 kcal/mol), followed by 6b and 6a, (−8.9 and −8.5 kcal/mol), respectively. The lowest recorded binding affinity was (−7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (−7.4 and −7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (−8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (−8.2 kcal/mol). The lowest reading was found for compound 3 ligand (−6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral M$^{pro}$. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1–4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1–3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds’ activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin

Studies with β-Oxoalkanonitriles: Simple Novel Synthesis of 3-[2,6-Diaryl-4- pyridyl]-3-oxopropanenitriles

Heteroaromatization of ethyl 2-cyano-4-oxo-2-(2-oxo-2-arylethyl)-4-arylbutanoates 3a,b with ammonium acetate gave ethyl 2,6-diarylisonicotinates 4a,b. Treatment of the latter with acetonitrile afforded novel β-oxoalkanonitriles 6a,b. Reactions of 6a,b with phenyl hydrazine and hydroxylamine gave the corresponding pyridyl aminopyrazoles 8a,b and pyridyl aminoisoxazoles 10a,b, respectively

Enaminones as Building Blocks for the Synthesis of Substituted Pyrazoles with Antitumor and Antimicrobial Activities

Novel N-arylpyrazole-containing enaminones 2a,b were synthesized as key intermediates. Reactions of 2a,b with active methylene compounds in acetic acid in the presence of ammonium acetate afforded substituted pyridine derivatives 5a-d. Enaminones 2a,b also reacted with aliphatic amines such as hydrazine hydrate and hydroxylamine hydrochloride to give bipyrazoles 8a,b and pyrazolylisoxazoles 9a,b, respectively. On the other hand, treatment of 2a,b with a heterocyclic amine and its diazonium salt yielded the respective [1,2,4]triazolo[4,3-a]pyrimidines 12a,b and pyrazolylcarbonyl[1,2,4]triazolo-[3,4-c][1,2,4]triazines 14a,b. Moreover, 2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (17) was prepared via reaction of enaminone 2a with aminothiouracil (15). Cyclocondensation of 17 with the appropriate hydrazonoyl chlorides 18a-c gave the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 21a-c. The cytotoxic effects of compounds 2b, 14a and 17 against human breast cell line (MCF-7) and liver carcinoma cell line (HEPG2) were screened and in both lines they showed inhibition effects comparable to those of 5-fluorouracil, used as a standard. The antimicrobial activity of some products chosen as representative examples was also evaluated

Cellulose Sulfuric Acid as an Eco-Friendly Catalyst for Novel Synthesis of Pyrido[2,3- d

A novel synthesis of a series of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones has been developed from reactions of 1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-3-arylprop-2-en-1-ones and 7-amino-1,3-disubstituted[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones in dioxane under thermal conditions, using cellulose sulfuric acid as an eco-friendly acid catalyst. The reaction mechanism was proposed and the structures of the newly synthesized compounds were established on the basis of spectral data (mass spectrometry, infrared, 1H and 13C nuclear magnetic resonance) and elemental analyses

Chitosan-MgO Nanocomposite: One Pot Preparation and Its Utility as an Ecofriendly Biocatalyst in the Synthesis of Thiazoles and [1,3,4]thiadiazoles

A chitosan-MgO hybrid nanocomposite was prepared using a simple chemical precipitation method and characterized using Fourier transform spectroscopy (FTIR), elemental analysis (EDX), and scanning electron microscopy (SEM). The nanocomposite was served as a powerful ecofriendly basic catalyst under microwave irradiation in the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 4a⁻j and 2-hydrazono[1,3,4]thiadiazoles 8a⁻d, incorporating a sulfonamide group. The structures of the synthesized products were elucidated by spectral data and elemental analyses. Also, their yield percentages were calculated using triethylamine (as a traditional catalyst) and chitosan-MgO nanocomposite (as a green recyclable catalyst) in a comparative study

Studies with β-Oxoalkanonitriles: Simple Novel Synthesis of 3-[2,6-Diaryl-4- pyridyl]-3-oxopropanenitriles

molecule