Synthesis of novel d-α-galactopyranosyl-l-seryl/l-threonyl-l-alanyl-l-alanine as useful precursors of new glycopeptide antibiotics with computational calculations studies.

New, simple, synthetic routes for the preparation of novel glycopeptide antibiotics are described. The structures of the synthesized compounds are elucidated by IR, two-dimensional NMR spectroscopy, and mass spectrometry. The stability of the new glycopeptide derivatives 10a,b is confirmed by assessing the physical character, HOMO-LUMO gap energy, ESP, and the corresponding correlation of 2D-NMR analysis. Furtherly, the target precursors are investigated via the DFT/B3LYP/6-311(G) basis set.

Synthesis, Characterization, and Biological Evaluation of Some Novel Pyrazolo[5,1-b]thiazole Derivatives as Potential Antimicrobial and Anticancer Agents.

The pharmacological activities of thiazole and pyrazole moieties as antimicrobial and anticancer agents have been thoroughly described in many literature reviews. In this study, a convenient synthesis of novel pyrazolo[5,1-b]thiazole-based heterocycles was carried out. The synthesized compounds were characterized by IR, 1H and 13C NMR spectroscopy and mass spectrometry. Some selected examples were screened and evaluated for their antimicrobial and anticancer activities and showed promising results. These products could serve as leading compounds in the future design of new drug molecules.

Synthesis, antiviral, DFT and molecular docking studies of some novel 1,2,4-triazine nucleosides as potential bioactive compounds.

A novel series of nucleosides with potential antiviral activity have been synthesized and characterized using IR, MS, 1D NMR and 2D NMR data. The antiviral activity of the synthesized compounds was assessed against the Coxsackie B virus and Hepatitis A virus (HAV-10). The results revealed that compound 6 is equipotent to the standard drug Ribavirin against HAV-10. Also, some computational studies, such as the prediction of pharmacokinetic properties, toxicity, and bioactivity, have been done.

Spiro Heterocyclic Compounds as Potential Anti-Alzheimer Agents (Part 2): Their Metal Chelation Capacity, POM Analyses and DFT Studies.

BACKGROUND: One of the best methods to treat Alzheimer disease (AD) is through the effective use of cholinesterase inhibitors as vital drugs due to the identification of acetylcholine deficit in the AD patients. OBJECTIVE: The present study aims the investigation of spiro heterocyclic compounds as potential AD agents supported by their metal chelation capacity, POM analyses and DFT studies, respectively. METHODS: The cholinesterase inhibition and metal chelation ability were performed on ELISA microtiter assay. Whereas, the B3LYP method with 6-31+G(d,p) basis set was implemented to study HOMOLUMO energy calculations. The pharmacokinetic properties of the synthesized molecules were studied through Petra, Osiris and Molinspiration (POM). RESULTS: The six spiro (1-6) skeletons were tested for their inhibitory potential and metal-chelation capacity. Our findings revealed that the tested spiro skeletons exerted none or lower than 50% inhibition against both cholinesterases, while compound 4 proved to be the most active molecule with 57.21±0.89% of inhibition toward BChE. The spiro molecule 3 exhibited the highest metal-chelation capacity (9.12±5.26%). Molecular docking model for the most active molecule exhibited promising bindings with AChE and BChE's active site pertained to hydrophobic hydrogen bonds and positive ionizable interactions. The POM analyses gave the information about the flexibility at the site of coordination of spiro compounds (1-6). CONCLUSION: The screening of spirocompounds (1-6) against cholinesterases revealed that some of them show considerable potential to inhibit AChE and BChE. Herein, we propose that the spiro molecules after further derivatization could serve interesting AD inhibitor drugs.

Computational studies of 2-(4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile.

The molecular structure of the 2-(4-oxo-3-phenylthiazolidin-2-ylidene) malononitrile (3) is calculated using DFT B3LYP/6-311G(d, p) method. The calculated geometric parameters are in good agreement with the experimental data. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and study the different intramolecular charge transfer (ICT) interactions occurring in the studied system. The BD(2)C17-C19 → BD*(2)C14-C15, LP(2)O2 → BD*(1)N5-C9 and LP(1)N5 → BD*(2)C10-C11 ICT interactions causing stabilization of the system by 23.30, 30.63 and 52.48 kcal/mol, respectively. The two intense electronic transition bands observed experimentally at 249 nm and 296 nm are predicted using the TD-DFT calculations at 237.9 nm (f = 0.1618) and 276.4 nm (f = 0.3408), respectively. These electronic transitions are due to H-3 → L (94%) and H → L (95%) excitations, respectively.

A novel synthesis, X-ray analysis and computational studies of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)- 4-oxo-3-phenylthiazolidin-2-ylidene)acetate as a potential anticancer agent.

BACKGROUND: 4-Thiazolidinone ring is reported to have almost all types of biological activities. Also, it present in many marketed drugs. RESULTS: Ethyl acetoacetate reacted with phenyl isothiocyanate and ethyl chloroacetate in presence of K2CO3 and DMF to afford the thiazolidinone derivative 5. Thiazolidinone 5 reacted with dimethylformamide-dimethylacetal to afford (Z)-ethyl 2-((Z)-5-((dimethylamino) methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate (6). The structure of thiazolidinone 6 was elucidated from its spectral analysis and X-ray crystallography and was optimized using B3LYP/6-31G(d,p) method. The geometric parameters and NMR spectra were discussed both experimentally and theoretically. Also, the natural charges at the different atomic sites were predicted. The synthesized compounds had moderate cytotoxic activity. CONCLUSIONS: An unexpected synthesis of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate via deacetylation mechanism. The structure was established using X-ray and spectral analysis. The geometric parameters, and NMR spectra were discussed. The synthesized compounds showed moderate anticancer activity.

Synthesis, X-ray Analysis, Biological Evaluation and Molecular Docking Study of New Thiazoline Derivatives.

A series of new thiazoline derivatives were synthesized. Structure analyses were accomplished employing 1H-NMR, 13C-NMR, X-ray and MS techniques. The in vitro antitumor activities were assessed against human hepatocellular carcinoma (HepG-2) and colorectal carcinoma (HCT-116) cell lines. The results revealed that the thiazolines 5b and 2c exhibited significant activity against the two cell lines. The in vitro antimicrobial screening showed that the thiazolines 2c, 5b and 5d showed promising inhibition activity against Salmonella sp. Additionally, the inhibition activity of thiazolines 2e and 5b against Escherichia coli was comparable to that of the reference compound gentamycin.

Synthesis and Biological Evaluation of Some Novel Thiazole-Based Heterocycles as Potential Anticancer and Antimicrobial Agents.

A novel series of thiazole-based heterocycles was synthesized using 1,3-dipolar cycloaddition reactions in the presence of chitosan-grafted-poly(vinylpyridine) as an eco-friendly biopolymeric basic catalyst. The molecular structure of the synthesized compounds was illustrated by spectroscopic and elemental analysis. Various in vitro biological assays were performed to explore the potential antitumor, antimicrobial and hepatoprotective activities of the newly synthesized compounds. The cytotoxic activities were assessed against human hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116) and breast cancer (MCF-7) cell lines and results revealed that all compounds displayed antitumor activities with the chlorine-containing derivatives, 11c and 6g, being the most potent. The majority of the tested thiazole derivatives exhibited satisfactory antibacterial activity towards the used gram positive and gram-negative bacterial species. Moreover, many derivatives showed weak hepatoprotective activity against CCl4-induced hepatotoxicity.

Eco-Friendly Synthesis, Characterization and Biological Evaluation of Some Novel Pyrazolines Containing Thiazole Moiety as Potential Anticancer and Antimicrobial Agents.

The one-pot synthesis of a series of pyrazoline derivatives containing the bioactive thiazole ring has been performed through a 1,3-dipolar cycloaddition reaction of N-thiocarbamoylpyrazoline and different hydrazonoyl halides or α-haloketones in the presence of DABCO (1,4-diazabicyclo[2.2.2] octane) as an eco-friendly catalyst using the solvent-drop grinding method. The structure of the synthesized compounds was elucidated using elemental and spectroscopic analyses (IR, NMR, and Mass). The activity of these compounds against human hepatocellular carcinoma cell line (HepG2) was tested and the results showed that the pyrazoline 11f, which has a fluorine substituent, is the most active. The antimicrobial activities of the newly synthesized compounds were determined against two fungi and four bacterial strains, and the results indicated that some of the newly synthesized pyrazolines are more potent than the standard drugs against test organisms.

Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

BACKGROUND: The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. RESULTS: Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. CONCLUSIONS: Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

A facile synthesis and anticancer activity of some novel thiazoles carrying 1,3,4-thiadiazole moiety.

BACKGROUND: Thiazoles and 1,3,4-thiadiazoles have been reported to possess various pharmacological activities. RESULTS: A novel series of thiazoles carrying 1,3,4-thiadiazole core were designed and prepared via the reaction of the 2-(4-methyl-2-phenylthiazole-5-carbonyl)-N-phenylhydrazinecarbo-thioamide with the appropriate hydrazonoyl chlorides. The structures of the newly synthesized compounds were confirmed based on elemental and spectral analysis as well as their alternative syntheses. The cytotoxic potency of the newly synthesized thiadiazoles was evaluated by their growth inhibitory potency in liver HepG2 cancer cell line. Also, the structure activity relationship was studied. CONCLUSIONS: All the newly synthesized compounds were evaluated for their anticancer activity against liver carcinoma cell line (HepG2) using MTT assay. The results revealed that the compounds 12d, 12c, 6g, 18b, 6c, and 6f (IC50 = 0.82, 0.91, 1.06, 1.25, 1.29 and 1.88 µM, respectively) had good antitumor activity against liver carcinoma cell line (HepG2) when compared with the standard drug Doxorubicin (IC50 = 0.72 µM). Graphical abstract A facile synthesis and anticancer activity of some novel thiazoles carrying 1,3,4-thiadiazole moiety.

A facile access and evaluation of some novel thiazole and 1,3,4-thiadiazole derivatives incorporating thiazole moiety as potent anticancer agents.

BACKGROUND: Many heterocyclic compounds containing thiazole or 1,3,4-thiadiazole ring in their skeletons have been reported to possess various pharmacological activities especially anticancer activities. RESULTS: 4-Methyl-2-phenylthiazole-5-carbohydrazide (2) was used as a synthon to prepare 2-(4-methyl-2-phenylthiazole-5-carbonyl)-N-phenylhydrazinecarbothioamide (3) and 2-(2-(4-methyl-2-phenylthiazole-5-carbonyl)hydrazono)-N'-phenylpropane hydrazonoyl chlorides 5a-c. In addition, thioamide 3 was used as starting material for preparation of a new series of thiadiazole derivatives via its reaction with hydrazonoyl chlorides 5a-c in dioxane using triethylamines as catalyst. In addition, a series of thiazole derivatives was synthesized by reaction of thioamide 3 with a number of α-halo compounds, namely, 3-chloropentane-2,4-dione (8) or 2-chloro-3-oxo-N-phenyl butanamide (10) phenacyl bromide 12 ethyl chloroacetate (14) in EtOH in the presence of triethylamine. The structures assigned for all the new products were elucidated based on both elemental analyses and spectral data and the mechanisms of their formation was also discussed. Moreover, the new products was evaluated in vitro by MTT assays for their anticancer activity against cell lines of Hepatocellular carcinoma cell line (HepG-2). The best result observed for compounds 7b (IC50 = 1.61 ± 1.92 (µg/mL)) and 11 (IC50 = 1.98 ± 1.22 (µg/mL)). The structure-activity relationships have been suggested based on their anticancer results. CONCLUSIONS: A novel series of new pharmacophores containing thiazole moiety have been synthesized using a facile and convenient methods and evaluated as potent anticancer agents.

Synthesis and Evaluation of Curcuminoid Analogues as Antioxidant and Antibacterial Agents.

Diazocoupling reaction of curcumin with different diazonium salts of p-toluidine, 2-aminopyridine, and 4-aminoantipyrine in pyridine yielded the arylhydrazones 2a-c. Arylhydrazone of p-toluidine reacted with urea, thiourea, and guanidine nitrate to produce 5,6-dihydropyrimidines. Further reaction of 2a with 2,3-diaminopyrdine in sodium ethoxide solution yielded 1H-pyrido[2,3-b][1,4]diazepine derivative. Bis(2,5-dihydroisoxazole) is obtained from the reaction of 2a with hydroxylamine hydrochloride, while its reactions with hydrazines afforded the respective 4,5-dihydro-1H-pyrazoles. The target compounds were evaluated as antioxidant and antibacterial agents. The tested compounds showed good to moderate activities compared to ascorbic acid and chloramphenicol, respectively.

One Pot Single Step Synthesis and Biological Evaluation of Some Novel Bis(1,3,4-thiadiazole) Derivatives as Potential Cytotoxic Agents.

A novel series of bis(1,3,4-thiadiazole) derivatives were synthesized in one step methodology with good yields by condensation reaction between bis-hydrazonoyl chloride 1 and various reagents. The structures of the prepared compounds were confirmed by spectral data (IR, NMR, and MS), and elemental analysis. The anticancer activity against human breast carcinoma (MCF-7) cancer cell lines was evaluated in MTT assay. The results revealed that the bis-thiadiazole derivatives 5c,d, 7b,c and 9c had higher antitumor activity than the standard drug Imatinib.