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Molecular docking simulation and synthesis of five compounds of N2, N4-bis (2-(4-substituted phenyl)-4-oxothiazolidin-3-yl)-3,5-dimethyl-1H-pyrrole-2,4-dicarboxamide was carried out to evaluate their theoretical binding affinities, targeting acute myeloid leukemia (AML). The chemical structure of the molecules was accurately drawn using ChemDraw Professional 19.1 software. The designed compounds were evaluated for their selectivity towards FLT3's ATP pocket (PDB ID:6JQR) in comparison with the reference ligand (Gilteritinib) by using GOLD suite from the Cambridge Crystallographic Data Centre (CCDC) software (Version 2021.2.0). All the designed compounds exhibited good binding energies with the receptor active pocket and had promising activity. Compounds 2E and 3E showed the highest PLP Fitness (83.30, 80.86 respectively) and it is higher than that of Gilteritinib (71.91). In-silico ADME and drug-likeness studies were performed by using the Swiss ADME server. The results showed that most of the designed compounds expected to be absorbed from the GIT. Compounds 2B-E have high expected GI absorption. All the investigated compounds have no predicted BBB penetration. Additionally, compounds 2A, 2C, 2D, and 3A are not a substrate to P-gps which may indicate a lower expected incidence of resistance by cancer cells in vitro studies. Finally, all of the investigated compounds are not considered to inhibit CYP1A2 enzyme, except for compounds 2A and 3D.

A series of novel 1,3-diazetidin-2-one derivatives were designed, synthesized, and evaluated preliminary (In Vitro) for their cytotoxic activity against the lung (A549) cancer cell line. GOLD software (version 2021.2.0) was used to conduct a molecular docking study; the tested derivatives demonstrated significant anticancer activity compared to the reference drug (erlotinib). PLP-fitness values for the final compounds are 79.81, 80.80, and 81.57, respectively, whereas the reference ligand, erlotinib, had a value of 76.20. The synthesized compounds were identified and characterized using physicochemical parameters (melting points and Rf values), FTIR, 1H-NMR, and 13C-NMR spectroscopy. According to the IC50 values for the synthesized derivatives, compounds N4a and N4b exhibit outstanding anti-proliferative activity with IC50 value of (7.51, 7.68) µM against A549 cell line, compared to erlotinib, which has an IC50 value of (11.5) µM.

A series of eight novels' 1,3-diazetidin-2-ones have been proposed to assess their potential activities. They are intended to examine antiproliferative effects through inhibition of epidermal growth factor receptor (EGFR) expression. These eight compounds strongly interact with the EGFR protein, responsible for the activity. As part of a present study, these compounds were docked to the crystal structure of the EGFR (Protein Data Bank code: 1 M17) to determine their binding affinity at the active site. Based on computer predictions, two compounds were demonstrated high scores of 80.80 and 85.89. After analyzing ADME properties, these compounds were found to have significant potential for binding. Consequently, the abilities of gefitinib, erlotinib, imatinib, and sorafenib were selected for comparison as controls. Computational methods were performed to predict the critical disposition of eight novels' 1,3-diazetidin-2-one derivatives to the EGFR. Moreover, a docking technique employing the Genetic Optimization for Ligand Docking program was conducted. Compounds 2 and 7 demonstrate a high docking peace-wise scoring function (PLP) fitness of 85.89 and 80.80, respectively. They fulfilled the Lipinski's rule, topological descriptors, and fingerprints of drug-like molecular structure keys. These compounds can be used as lead compounds to develop novel antiproliferative agents. The outcome of applying this study is novel series of 1,3-diazetidin-2-one compounds as new analogs were designed and evaluated for their antiproliferative activity with a higher potency profile and binding affinity within the active sites of EGFR.

This review is about 1,2,4-triazoles include their synthesis; their physio-chemical properties, SAR, reactions, derivatives. Finally, their biological activities with a demonstrated showing different requirements to achieve different activity

Infections caused by bacteria have a significant impact on public health. Chemical synthesis of new derivatives of cephalexin inked to amino acid (tryptophan or histidine) through an amide bond at the acyl side chain is achieved. This is a new approach of incorporating, tryptophan and histidine into the the primary amino group of cephalexin, in order to provide a bulky group very close to the β-lactam ring. This chemical addition act as isosteric group to the alkoximino that protect beta lactam ring from bacterial beta lactamase enzyme. The new derivatives may show resistance to β-lactamases, improve activity and pharmacokinetic properties and may give new life for old drugs that are susceptible to hydrolysis by most β-lactamases. The chemical structures of these derivatives were confirmed by: FTIR, 1H-NMR spectroscopy, elemental micro analysis and some physical properties. Molecular docking on serine beta lactamase and prediction of ADME parameters were recorded using GOLD suite and Swiss ADME software respectively. Docking scores of the new derivatives of Cephalexin on β-lactamases were higher than those of Cephalexin, which may indicate better activity

New two derivatives of 2- methyl benzoimidazole were designed, synthesized and evaluated as a potential cyclooxygenase-2 [COX-2] inhibitors. The synthesized compounds have been recognized according to their spectral FT-IR, 1H-NMR data and physical pro- perties. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using egg-white stimulated paw edema method with respect to the effect of propylene glycol 50%v/v [control group] and the ibuprofen [10mg/kg i.p.] was selected as a reference ligand. New compounds showed a significantly higher in vivo anti-inflammatory activity compared with ibuprofen as a reference drug. COX-2 selectivity evaluation through molecular docking via GOLD suite [v. 5.6.2.]. The new compounds via molecular docking showed significant higher activities when compared with ibuprofen as referenced drugs because of having hydrogen bonding interaction toward the key amino acids within COX-2 structure and all these results were compatible with the study of in vivo acute anti-inflammatory activities for tested compounds. ADME studies were performed to predict absorption, bioavailability, topological polar surface area, and drug-likeness. The results of ADME studies showed that all synthesized compounds absorbed from the gastrointestinal tract.

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds are evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxen

This research involves preparation of many bisheterocycles attached to pyrrole rings have been synthesized by the stepwise procedure such asbis(1,2-dihydropyridazine-3,6-dione) (3),bis(2,3dihydrophthalazine-1,4-dione) (4) and bis(tetrahydropyridazine-3,6-dione) (5) derivatives of pyrrole. Further the bis(3,5-dimethyl-1H-pyrazol-1-yl)methanone (6), bis(3-methyl-1H-pyrazol5(4H)-one) (7) and bis(4H-1,3,4-oxadiazin-6(5H)-one) (8) pyrrole derivatives also prepared in good yields. Furthermore, series of bis-benzothiazine (10a-c), bis-benzoxathiazepine (11a-c)and bis-quinazoline compounds (12a-c) attached to pyrrole moieties also have been synthesized successfully.Structures of the newly synthesized compounds were established by physicochemical, elemental analysis CHNS, FTIR, H-NMR and C-NMR spectroscopic methods. The new synthesized agents were evaluated for their in vitro inhibitory effectagainst several candida isolates. Some of the evaluated compounds possessed good activities compared to a fluconazole, nystatin and clotrimazole standard antifungal drugs.

A series of sulfamethoxazole derivatives attached to heterocyclic ring such as 1,2-diazepane (3), 1,3,4-oxadiazole (4), two pyrazoles (5,6), 1,2,4-triazine (7), 1,3,4-oxadiazine (8) and four novel 1,3-oxazepines (14-17)were designed and synthesized in this research. The structures of the newly prepared compounds were confirmedbased on a comprehensive characterization of spectral data by applied (infrared, proton and carbon nuclear magnetic resonance spectroscopy). Physicochemical properties also determined for each synthesized derivatives. The finallyprepared compounds were tested for their anti-bacterial and fungal activity invitro. Four types of pathogenic bacteria with two types of yeast similar to fungi were used in the evaluation. Each screened compounds showed perfect antimicrobial activity comparable with sulfamethoxazole used as parent drug

This research include developing new heterocyclic derivatives of 1,8-naphthalimides bearing oxazoline, thiazoline, oxadiazole, thiadiazole and aminotriazole moieties as the following steps: N-ester-1,8-naphthalimide (1) was obtained by direct imidation of 1,8- naphthalic anhydride with ethylglycinate in dimethylsulfoxide. Compound (1) was treated with hydrazine hydrate in absolute ethanol to give N-acetohydrazide-1,8-naphthalimide (2). N-Acetophenylsemicarbazide-1,8-naphthalimide (3) and N-Aceto phenylthiosemicarbazide- 1,8-naphthalimide (7) were synthesized via reaction of compound (2) with phenylisocyanate and phenylisothiocyanate in absolute ethanol respectively. Cyclization of compounds (3) and (7) with p-substituted phenacyl bromide gives the oxazoline derivatives (4-6) and thiazoline derivatives (9-11) respectively. N-Methyl-[(5- (phenyl amino)-1,3,4-thiadiazol-2-yl)]-1,8-naphthalimide (8) prepared via treatment of compound (7) with phosphoric acid. Reaction of the prepared hydrazide (2) with carbon disulfide in the presence of potassium hydroxide producing N-Methyl-[potassium dithiocarbazate]-1,8-naphthalimide (12). Acidifying of the obtained salt (12) with 4N hydrochloric acid give N-Methyl-[1,3,4-oxadiazol-2-yl-5-thiol]-1,8-naphthalimide (13). The obtained salt (12) also treated with hydrazine hydrate to afford the desirable N-Methyl-[1,2,4- triazol-3-yl-4-amino-5-thiol]-1,8-naphthalimide (14). All the prepared compounds in this research were characterized by recording their melting points, FTIR, 1HNMR, 13CNMR spectra, checked by TLC, physical properties and some specific chemical tests also. Some of the new prepared compounds were evaluated for the antimicrobial screening in vitro against two types of Gram positive bacteria including (Staphylococcus aureus, Bacillus subtilis) and two types of Gram negative bacteria including (Escherichia coli, Pseudomonas aeuroginosa). More, antifungal activities of some prepared compounds performed against the yeastlike pathogenic fungus (Candida albicans). The antimicrobial screening carried out in three concentrations of prepared compounds. Sulfamethoxazole/Clotrimazole was used as standard drugs. The results showed that most of the tested compounds have good biological activity against the mentioned organisms compared with standard drugs above