Synthesis of Novel Quinazoline Derivatives as Antimicrobial Agents

Quinazoline isothiocyanate 1 reacts with various nucleophiles(nitrogen nucleophiles,oxygen nucleophiles and sulphur nucleophiles)to afford heterocyclic systemes 2-13,Also,the [4 2] cycloaddition reaction of 1 with phenyl isocyanate,benzylidene aryl amine and cinnamic acid derivatives gave novel heterocyclic compounds 14-16,Moreover,the reaction of 1 with active methylene compounds under Michael reaction conditions also was investigated to yield 17 and 18 and it was found that all these reactions proceede via isothiocyanate heterocyclization to furnish non-condensed heterocyclic compoundes,Some of the newly synthesized compounds were tested for their antimicrobial activities.     

1,5-Benzothiazepine Derivatives: Green Synthesis,In Silico and In Vitro Evaluation as Anticancer Agents

Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol-400 (PEG-400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG-400. PEG-400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a–2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase-3β, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G-2, with an IC₅₀ of 3.29 ± 0.15 µM, whereas the standard drug IC₅₀ was 4.68 ± 0.17 µM. In the prostate cancer cell line DU-145, the compounds displayed IC₅₀ ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an IC₅₀ of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives.     

Design,Synthesis, and Biological Evaluation of 1,2,4-Oxadiazole-Isoxazole Linked Quinazoline Derivatives as Anticancer Agents

Russian Journal of General Chemistry - A series of novel 1,2,4-oxadiazole-isoxazole linked quinazoline compounds is designed, synthesized and screened for anticancer activity on four human cancer...     

Synthesis and Application of Some New Thienopyrimidine Derivatives as Antimicrobial Agents

The paper describes the synthesis of new ring system 5-phenylthieno[2,3-d]pyrimidine-4(3H)one (2). Chlorination of (2) with PCl₅, POCl₃ gave the corresponding 4-chloro derivative (4). Several derivatives of the latter compound have been synthesised and tested for antimicrobial activity.     

Design,Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.     

Synthesis and Antimicrobial Activity of Some Annelated Quinazoline Derivatives

A highly efficient and versatile synthetic approach to the synthesis of annelated quinazoline derivatives viz 1,2,4‐triazino[4,3‐c]quinazoline 5–7 , 11 , thiazolidinylquinazoline 9 , quinazolino[4,3‐b]quin‐azolin‐8‐one 12 and imidazoquinazolines 14a,b,15 is presented. Also, a variety of pyrazolylquinazolines 19–21 and pyrimidinylquinazolines 22a,b were obtained via a sequence of heterocyclization reactions of 4‐methyl‐N‐[4‐(4‐oxo‐3,4‐dihydroquinazolin‐2‐yl)phenyl]benzene‐sulfonamide ( 2 ) with different reagents. The new compounds were synthesized with the objective of studying their antimicrobial activity.     

Synthesis of Some New Benzimidazole–Thiazole Derivatives as Anticancer Agents

4‐(1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐amine and its 1‐methyl derivative ( 1 ) were reacted with different reagents such as acid anhydrides, malononitrile, chloroacetyl chloride, and aromatic aldehydes to produce the corresponding benzimidazole products 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , respectively. Also, 2‐chloro‐N‐(4‐(1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐yl) acetamide ( 6 ) was reacted with diaminoethane, ortho‐substituted aniline, thioglycolic acid, thiosemicarbazide derivatives, secondary amines, and potassium isothiocyanate to afford the corresponding derivatives 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , respectively. The cytotoxic activity of some newly synthesized derivatives was studied against two different cell lines HepG2 and PC12. Compounds 9 and 15b showed promising anticancer activity against both types of the tested cancerous cell lines.     

Synthesis of Thiazolidine and Thiophene Derivatives for Evaluation as Anticancer Agents

The non-isolated adducts (3a,b) were used as key intermediates to synthesize some novel thiazolidine and thiophene derivatives. Compound (4) exhibited a remarkable antitumor activity against EAC cells compared with the Doxorubicin as a positive control.     

Novel Pyridothienopyrimidine Derivatives: Design,Synthesis and Biological Evaluation as Antimicrobial and Anticancer Agents

The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives 2a,b–9a,b was synthesized via cyclization reactions of 3-amino-thieno[2,3-b]pyridine-2-carboxamides 1a,b with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (3a, 4a, 5a, 6b, 8b and 9b) were examined as EGFR kinase inhibitors. Molecular docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds 3a, 5a and 9b displayed broad spectrum antimicrobial activity with MIC ranges of 4–16 µg/mL and potent cytotoxic activity with IC₅₀ ranges of 1.17–2.79 µM. In addition, they provided suppressing activity against EGFR with IC₅₀ ranges of 7.27–17.29 nM, higher than that of erlotinib, IC₅₀ = 27.01 nM.     

Novel Quinazoline Derivatives Bearing a Sulfapyridine Moiety as Anticancer and Radiosensitizing Agents

Quinazoline derivatives posses many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There is a variety of mechanisms for their anticancer activity. The present work reports the possible utility of methyl anthranilate in the synthesis of some new quinazoline derivatives, bearing a substituted sulfonamide moiety. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human liver cancer cell line, using doxorubicin as a reference drug. In addition, the most active compounds 14 and 15 were selected and evaluated for their ability to enhance the cell killing effect of γ‐radiation.     

Design,Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors

Malignant tumor is one of the major diseases that seriously threaten human health today. Compared with traditional chemotherapy, targeted drug therapy has become a new idea of tumor therapy. And EGFR(epidermal growth factor receptor) is highly expressed in many human tumor cell lines, which is a biomarker of tumor proliferation. In this paper, small molecule tyrosine kinase inhibitors with quinazoline structure aiming at EGFR were studied. A series of novel quinazoline derivatives(4 a～4 l) have been designed and synthesized from 4-hydroxyquinazoline as the parent core. Structures of target compounds were characterized by ~1H NMR and ~(13)C NMR spectra. The in vitro anticancer activity of compounds 4 a～4 l was evaluated by MTT assay against Hela,MCF-7 and A549 tumor cell lines, and apoptosis-inducing capacity was investigated by Annexin-V/PI staining assay.The results showed that all compounds had good antitumor activity against the test tumor cell lines. Especially,compound 4 a exhibited the best anticancer activity(IC_(50) = 10.23 μM) against Hela cell lines, remarkable ability to induce apoptosis, and low toxicity, which identified 4 a as a promising anticancer drug aiming at EFGR.     

Synthesis and QSAR Study of Some Novel Heterocyclic Derivatives as In Vitro Cytotoxic Agents

2,3‐Diaryloxirane‐2,3‐dicarbonitriles have employed in heterocyclic synthesis in many organic reactions. Authors highlight its use as intermediate in the synthesis of various organic compounds through the reaction with different nitrogen nucleophiles as methyl hydrazine, thiourea, thiosemicarbazide, methylglycinate, and others to furnish new heterocyclic derivatives. They are also used as key starting materials to construct some important heterocycles. Structures of all newly synthesized products are substantiated by studying their micro analytical and spectral data. Some of newly synthesized compounds were evaluated for their in vitro cytotoxic effects against a panel of three human tumor cell lines, namely, Hep‐G2, Hela, and MCF‐7. Most of the newly synthesized compounds ( 1a , 2a , 2d , 3 , 4 , 5 , 6a , 6c , 6d , 7a , and 7b ) inhibited cell proliferation with IC₅₀ values in range of 0.52–5.21 μΜ. For activity against HepG2 cell line, compounds 5 , 6a , 6d , and 7b emerged as the most active members. The Hela cell line showed highest sensitivity toward compounds 2a , 2d , and 6c whereas compounds 2d and 6c showed the highest inhibitory activity against MCF‐7 cell line.     

Chromenol Derivatives as Novel Antifungal Agents: Synthesis,In Silico and In Vitro Evaluation

Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols (3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and the evaluation of their antifungal activity. In silico prediction of biological activity with computer program PASS indicate that the compounds have a high novelty compared to the known antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k, followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8 µM, respectively. Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular docking studies on C. albicans sterol 14α-demethylase (CYP51) and DNA topoisomerase IV were used to predict the mechanism of antifungal activities. According to the docking results, the inhibition of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We also showed that most active compounds have a low cytotoxicity, which allows us to consider them promising antifungal agents for the subsequent testing activity in in vivo assays.     

Synthesis and Antimicrobial Evaluation of Some New Spiroindolinone Derivatives

In an attempt to find a new class of antimicrobial agents, a series of spiroindolinone compounds containing pyridine, pyrimidine, benzopyrans, pyrido, naphtodiazepines, pyrazole, and isoxazole ring systems were prepared via the reaction of 3‐(2‐oxo‐2‐(3‐oxo‐3H‐benzo[f]chromen‐2‐yl)ethylidene)indolin‐2‐one ( 4 ) with an appropriate nucleophilic reagent. Newly synthesized compounds were characterized by elemental analysis and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). Representative compounds were tested and evaluated as antimicrobial agents.     

Synthesis and Antimicrobial Evaluation of Some New Thiophene Derivatives

2-(2-Cyano-acetylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxamide(3) was used as starting material for synthesis of 4-thiazolidinone, thiazolidine, and thiophene derivatives 6, 7a, b, and 8a, b, respectively. Thiocarbomyl derivative 5, 4-thizolidinone 9, and thioxothiazolidine 10 were obtained from reaction of 3 with thioglycolic acid and phenyl isothiocyanate/sulfur, respectively. Condensation of 3 with selected cyclic ketones and aromatic aldehydes yielded the arylidine derivatives 11a, b and 13, respectively. Refluxing of 11a, b with sulfur and morpholine yielded the thiophene derivatives 12a, b, respectively. Diazocoupling of compound 3 withp-tolyl diazonium chloride yielded the hydrazone derivative 14. The newly synthesized compounds were characterized by infrared, ¹H NMR, and mass spectral studies. Representative compounds of the synthesized product were tested and evaluated as antimicrobial agents. Compound 12b gives very high antimicrobial activity against Ampicillin.     

Synthesis and Biological Evaluation of Amide Derivatives of Imidazopyridine as Anticancer Agents

A series of new amide derivatives of imidazopyridine is synthesized and structures of the products are confirmed by ¹H and ¹³C NMR, and mass spectral data. The synthesized derivatives are screened for their anticancer activity against four human cancer cell lines: lung cancer (A549), breast cancer (MCF-7), melanoma cancer (A375), and colon cancer (HT-29). Six synthesized compounds exhibit more potent activity than the control drug.

     

Synthesis,Reactions, and Antimicrobial Evaluation of Some Polycondensed Thienopyrimidine Derivatives

Some novel indeno[2,1-b]thiophenes, indeno[1′,2′:4,5]thieno[2,3-d][1,2,3]triazines, indeno[1′,2′:4,5]thieno[2,3-d]pyrimidines, indeno[1′,2′:4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidines, and indeno[1′,2′:4,5]thieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 2–16 were prepared starting with 2-aminoindeno[2,1-b]thiophene-3-carboxylic acid amide ( 1 ). Furthermore, the antimicrobial evaluation of the prepared products showed that many of them revealed promising antimicrobial activity.