Oxadiazole Moieties Research Articles

Design, synthesis and herbicidal activity of novel sulfonylureas containing triazole and oxadiazole moieties

Three novel series of 5-substituted sulfonylurea derivatives were designed and synthesized via introducing a triazole or oxadiazole ring at the 5th position of the benzene ring in classical sulfonylurea herbicides. All the target compounds were confirmed by means of 1H nuclear magnetic resonance(NMR), 13C NMR and elemental analysis. The bioassay results show that the target compounds containing an oxadiazole ring at the 5th position display moderate to excellent herbicidal activities against Brassica campestris and Amaranthus retroflexus under soil treatment. Especially, compounds zdk20, zdk21 and zdk22 possess 98.6%, 96.5% and 94.5% inhibition rates, respectively, against Amaranthus retroflexus at a concentration of 75 g/ha(1 ha=1×104 m2) under soil treatment, which approach to those of the commercial herbicide chlorsulfuron.

Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity.

The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

Endothelium Dependent and Independent Mechanisms of Vasorelaxant Activity of Synthesized 2,5-disubstituted-1,3,4-oxadiazole Derivatives in Rat Thoracic Aorta - Ex vivo and Molecular Docking Studies

Background: Vasoconstriction is a major pathological feature of cardiovascular diseases involving endothelium dependent and independent mechanisms. Oxadiazole moiety appeared to be effective in various pathologies. Objective: The aim of the study was to synthesize and evaluate the mechanism of vasorelaxation exhibited by synthesized oxadiazole derivatives. Method: The 2,5-disubstituted-1,3,4-oxadiazole derivatives were synthesized by an efficient and simple method. The derivatives were investigated for their ex-vivo vasorelaxant action on intact/denuded endothelium rat aortic rings precontracted with norepinephrine/ phenylephrine/KCl. Results: The contractions induced in the aortic rings by the addition of cumulative concentrations of norepinephrine, phenylephrine, KCl and calcium were significantly antagonized by a derivative, OXD-Z2. In another experiment, verapamil pretreatment inhibited phenylephrine and Ca2+-induced aortic contractions and OXD-Z2 did not alter verapamilinduced inhibition. This indicated the role of L-type Ca2+-channels in the OXD-Z2-induced vasorelaxation via inhibition of calcium influx. Further, atropine (muscarinic receptor antagonist), L-NAME (NO synthase inhibitor) and methylene blue (non-selective cGMP inhibitor) inhibited OXD-Z2-induced relaxation in other sets of experiments. These results indicate that OXD-Z2 also mediates vasorelaxation through NO release by muscarinic receptor activation. In addition, the molecular docking studies showed that OXD-Z2 interacts with L-type Ca2+-channel, muscarinic (M2) receptor and eNOS. Conclusion: Thus, it is deduced from the above findings that the vasorelaxant activity of OXD-Z2 involves muscarinic receptor-mediated nitric oxide release in addition to direct inhibition of L-type Ca2+-channels. Keywords: 2, 5-disubstituted-1, 3, 4-oxadiazoles, aortic rings, endothelium, vasorelaxation, hypertension.

Synthesis of some new quinazolin-4(3H)-one derivatives and evaluation of their anticonvulsant activity

We reported the synthesis of a novel series of quinazolin-4(3H)-one derivatives bearing oxadiazole, thiadiazole, and other moieties in the 3-position of the quinazolinone nucleus using appropriate synthetic route. The compounds were evaluated for their anticonvulsant activity using picrotoxin model, GABA-A receptor antagonist. Five compounds showed significantly prolonged times for convulsions compared with the standard drug phenobarbital.

Structural Requirements and Docking Analysis of Amidine-Based Sphingosine Kinase 1 Inhibitors Containing Oxadiazoles.

Sphingosine 1-phosphate (S1P) is a potent growth-signaling lipid that has been implicated in cancer progression, inflammation, sickle cell disease, and fibrosis. Two sphingosine kinases (SphK1 and 2) are the source of S1P; thus, inhibitors of the SphKs have potential as targeted cancer therapies and will help to clarify the roles of S1P and the SphKs in other hyperproliferative diseases. Recently, we reported a series of amidine-based inhibitors with high selectivity for SphK1 and potency in the nanomolar range. However, these inhibitors display a short half-life. With the goal of increasing metabolic stability and maintaining efficacy, we designed an analogous series of molecules containing oxadiazole moieties. Generation of a library of molecules resulted in the identification of the most selective inhibitor of SphK1 reported to date (705-fold selectivity over SphK2), and we found that potency and selectivity vary significantly depending on the particular oxadiazole isomer employed. The best inhibitors were subjected to in silico molecular dynamics docking analysis, which revealed key insights into the binding of amidine-based inhibitors by SphK1. Herein, the design, synthesis, biological evaluation, and docking analysis of these molecules are described.

Synthesis of New 1,2,4-Triazoles Containing Oxadiazole Moiety: Potential Intermediates for Preparation of Ribavirin Analogues

Synthesis of New 1,2,4-Triazoles Containing Oxadiazole Moiety: Potential Intermediates for Preparation of Ribavirin Analogues

Synthesis, Characterization and Antioxidant Activity of Carvacrol Containing Novel Thiadiazole and Oxadiazole Moieties

Carvacrol is a well-known antioxidant found in the extract of various angiospermic plants. The purpose of present research is to synthesize new carvacrol derivatives associated with heterocycles namely 1,3,4-thiadiazole and 1,3,4-oxadiazole to explore their extraordinary potential in medicine and agriculture. Structures of newly synthesized compounds were confirmed by spectroscopic techniques such as FT-IR, 1H and 13C NMR and LC-MS. Finally, synthesized derivatives were evaluated for their in-vitro antioxidant activity by using radical scavenger DPPH assay. All the compounds exhibited remarkable antioxidant activity, out of which compound showed better or similar antioxidant activity compared to standard compound ascorbic acid.

Electronic alteration of end-on phenyl groups of bis-triazolyl-silanes: electron-transport materials for blue phosphorescent OLEDs

Electron transporting ability is controlled by alternating electronic properties of peryphery groups on silicon based oxadiazole moiety.

Rational design of methacrylate monomers containing oxadiazole moieties for single‐layer organic light emitting devices

ABSTRACTMethacrylate derived monomers functionalized with pendant oxadiazole moieties were synthesized and copolymerized with carbazole containing monomers to form polymers with electron and hole transporting fragments in the same molecule. Substituents on the oxidazole moiety were varied with the purpose of bandgap tuning and performance optimization when employed in single‐layer organic light emitting devices (OLED). Quantum mechanical calculations of the HOMO‐LUMO levels of the oxidazole derivatives were used to down‐select promising candidates for chemical synthesis and testing in single‐layer OLEDs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 1663–1673

Design, synthesis, molecular modeling and anti-breast cancer activity of novel quinazolin-4-one derivatives linked to thiazolidinone, oxadiazole or pyrazole moieties

6,8-Dibromo-2-(4-chlorophenyl)-quinazolin-4-one linked directly to oxadiazole 5, pyrazole 6 or through amide linkage to thiazolidinone 2a–d and 3a–h were synthesized; their chemical structures were confirmed by spectral and elemental analyses. Their anti-breast cancer activity was evaluated against human breast cancer cell line (MCF-7) using resazurin reduction method and doxorubicin as a reference drug. Linking quinazolin-4-one scaffold to oxadiazole or pyrazole gave compounds 5 and 6 with a closely similar activity as doxorubicin; their IC50 was 23, 22 and 22 nmol/ml, respectively; however, the hybridization of quinazolin-4-one with thiazolidinone gave much better activity than doxorubicin. The most active compounds of the hybrid molecules between quinazolin-4-one and thiazolidinone are 2c,d and 3a,f. Their IC50 range was (3–9 nmol/ml). In an attempt to explore the mode of action of the best active compounds, docking on the ATP binding site of EGFR was performed. In vitro screening of these four compounds against EGFR tyrosine kinases showed inhibitory activity range 54–77.2 %.

Synthesis, Spectroscopic Characterization and Powder XRD Study of 4-(5-(Ethylthio)-1,3,4-Oxadiazole-2-yl) Aniline

In order to investigate the separation mechanism of liquid crystals stationary phases based on an oxadiazole moiety, new 1,3,4-oxadiazole derivative as side mesogenic arm in liquid crystals was prepared, and its structural spectroscopic data were studied in this paper. A powerful indication about the relationship between molecular structure and alignment properties is described. Such information is indispensable for the design and synthesis new liquid crystals stationary phases of high separation efficiency.

Synthesis, Characterization and Antimicrobial Screening of Some Bioactive 1,8-Naphthalimide Derivatives.

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

Synthesis and Biological Evaluation of a New Series of Pyrazolines as New Anticandidal Agents

New pyrazoline derivatives bearing an oxadiazole moiety were synthesized via the reaction of 1-(chloroacetyl)-3-(2-furyl/thienyl)-5-aryl-2-pyrazolines with 5-substituted-1,3,4-oxadiazole-2(3H)-thiones in the presence of potassium carbonate. Compounds 1 – 32 were screened for their antifungal activity against various Candida species and compared with ketoconazole. Among these compounds, the most effective derivatives were evaluated for their cytotoxicity against NIH/3T3 cells. 2-({2-[5-(4-Bromophenyl)-3-(2-furyl)-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl}thio)-5-(2-cyclopentylethyl)-1,3,4-oxadiazole (23) can be identified as the most potent antifungal agent against C. tropicalis due to its inhibitory effect on C. tropicalis and low toxicity to NIH/3T3 cells.

Activity of IQG-607, a new orally active compound in a murine model of Mycobacterium tuberculosis infection

Tuberculosis (TB) caused by Mycobacterium tuberculosis, remains a major global health concern. According to the World Health Organization (WHO), TB was responsible for the occurrence of 1.8 million deaths in 2012 [1], and currently represents the main cause of human death due to a single pathogen. Increasing HIV-TB co-infections, the emergence of multidrug-resistant (MDR) [2,3], extensively drug-resistant(XDR) [3,4], and, more recently, of totally drug resistant strains (TDR) [5] have increased the need for developing new drugs to treat TB. Globally, 3,7% of new TB cases and 20% of previously treated patients are estimated to have MDR-TB [2] Ideally, novel anti-Tb drugs, should be effective against the resistant strains, decreasing the length of treatment thereby improving patients compliance with lower dose frequency, minimal drug-drug interactions and reduced toxicity issues [1,3]. Isoniazid (INH) is the most prescribed drug for active TB and prophylaxis. It has been demonstrated that its primary target is the M. tuberculosis 2-trans-enoyl-ACP (CoA)reductase enzyme (inhA) [4]. Furthermore, INH is s pro-drug, activated by the mycobacterial KatG-encoded catalase-peroxidase enzyme in the presence of manganese ions, NAD(H) and oxygen [5]. Unfortunately, the use of INH has been allied to a series of collateral effects, especially neurotoxic and hepatotoxic side effects [6]. Our group has described a new approach to the rational design of an INH analogue based on an inorganic group (a pentacyanoferrate III/II) attached to the nitrogen atom of the heterocyclic ring of INH, which inhibits the validate target inhA [6,7]. The metal center of the compound can promote an electron transfer reaction that mimics the in vitro activation of INH by KatG enzyme. In fact, our group has also proved that this new compound pentacyano(isoniazid)ferrate(II) (named IQG-607), does not require the activation by katG or any other enzyme to bind to its orimary target the M. tuberculosis inhA [7,8]; this profile might help to overcome an important mechanism of INH-resistance, the missense mutations in the katG gene. Moreover, our group has demonstrated that the compound IQG-607 is able to inhibit in vitro activity of wild-type and INH-resistant I21V,I47T and S94A M. tuberculosis inhA mutant enzymes more slowly than INH [8,10]. Slow rates of dissociation are expected when we intend to reach higher inhibitory effectiveness and, therefore, the intervals between the doses administered to patients can be longer. Noteworthy, another new compound containing a pentacionaferrate and an oxadiazole moiety, pentacyano(2-metil-5-(piridin-4-il)-1,3,4-oxadiazole)ferrate (II), (named IQG-639) was also found to be able to inhibit the in vitro activity of wild-type and INH resistant (S94A) M. tuberculosis inhA enzymes. Other experiments demonstrated that both IQG-607 and IQG-639 were active against culture of M. tuberculosis H37Rv and two INH-resistant clinical isolates, showing satisfactory efficacy in vitro. Importantly, we have established toxicological parameters in mice to determine the safety of both compounds and to guide us in the next in vivo tests. Furthermore,90 days repeated-doses toxicological studies in rats revealed a very favorable outcome for IQG-607 which was also very active in mouse macrophages infected with M. tuberculosis. It thus appears warranted to examine the potential in vivo anti-TB activity of these two compounds, IQG-607 and IQG-639. Accordingly, the activity of these compounds was evaluated by using an in vivo murine model of tuberculosis infection. Swiss mice were infected with M. tuberculosis H37Rv strain and IQG-607 and IQG-639 (250mg/kg) were administered during 28 or 56 days. A dose response study was also performed with IQG-607 at 5, 10, 25, 100, 200 and 250mg/kg. The activity of test compound was compared with that of positive control drug INH at 25 mg/kg. After either 28 or 56 days of treatment, both IQG-607 and INH significantly reduced M. tuberculosis-induced splenomegaly, and also significantly diminished the colony forming units (CFU) in both spleens and lungs. IQG-607 or INH ameliorated the lung macroscopic aspect, reducing the lung lesions (granuloma like) to a similar extent [9]. However, IQG-639 was not capable or significantly modifying any evaluated parameters. In addition, experiments using early and late controls of infection revealed a bactericidal activity for IQG-607 in the animal model of infection. The promising activity of IQG-607 in M. tuberculosis-infected mice brings the hope that this compound might represent a good candidate for clinical development as a new antimycobacterial agent. Experiments to demonstrate efficacy and security in dogs and mini-pigs are under way.

Oxadiazole-2-thiol adsorption on gold nanorods: a joint theoretical and experimental study by using SERS, XPS, and DFT.

The chemisorption of 1,3,4-oxadiazole-2-thiol (ODT) on gold nanorods has been investigated by using surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT). Although most of the SERS spectra have remarkable similarity to the normal Raman spectra of the pure analyte, the adsorption of ODT on a gold surface leads to a drastic change in its Raman spectrum and distinct vibrational features are obtained with gold nanorods and spherical nanoparticles. Simulated Raman spectra for hybrid systems that consist of an oxadiazole moiety coordinated to a Au20 gold cluster provided valuable information about the coordination mode and enabled us to assign vibration modes.

A mini review on pharmacological activities of oxadiazole and thiadiazole compounds

In the last few years, heterocyclic compounds have attracted strong interest and a lot of work has been done on oxadiazole and thiadiazole ring. Oxadiazole and thiadiazole a five member heterocyclic nucleus has attracted a wide attention of the chemist in search for the new therapeutic agents. Various different oxadiazole and thiadiazole compounds have been prepared and possess useful pharmacological activities. Both oxadiazole and thiadiazole derivatives possess a wide range of pharmacological activities such as anticancer, anticonvulsant, antimicrobial, anti-inflammatory, antioxidant, antitubercular, antimalarial, antinociceptive etc. This review contains various pharmacological activities of oxadiazole and thiadiazole derivatives and it is the milestone for the new research towards oxadiazole and thiadiazole moiety.

Synthesis, Characterization and study biologicalactivity of several 1-cyclopentene-1,2-dicarboxylimidyl Containing oxadiazole and Benzothiazole

In this work involved prepared of several new 1-cyclopentene-1,2-dicarboxylimide linked to oxadiazole and benzothiazole moiety were synthesized by two steps: The first step 2-amino-substituted-1,3,4-oxadiazoles and substituted-2-aminobenzothiazole were reaction with 1-cyclopentene-1,2-dicarboxyl anhydride producing N-( 5- substituted-1,3,4-oxadiazole-2-yl)-1-cyclopentene-1,2-dicarboxyl amic acids and N-(Substitutedbenzothiazole-2-yl)-1-cyclopentene-1,2-dicarboxyl amic acids which in turn were dehydrated in the second step via fusion method to afford he desirable N-(5-substituted-1,3,4-oxadiazole-2-yl)-1-cyclopentene-1,2-dicarboxylimides and N-(Substituted benzothiazole-2-yl)1-cyclopentene-1,2-dicarboxylimides respectively. Structures of the prepared compounds were characterized by depending on FTIR, U.V spectral data which were in agreement with the proposed ones. Finally antibacterial activity of some of the prepared new cyclic imides were studied by two types of bacteria and the results showed that the most of the tested imides posses good biological activity against these bacteria.

Synthesis, Characterization and study biologicalactivity of several 1-cyclopentene-1,2-dicarboxylimidyl Containing oxadiazole and Benzothiazole

In this work involved prepared of several new 1-cyclopentene-1,2-dicarboxylimide linked to oxadiazole and benzothiazole moiety were synthesized by two steps: The first step 2-amino-substituted-1,3,4-oxadiazoles and substituted-2-aminobenzothiazole were reaction with 1-cyclopentene-1,2-dicarboxyl anhydride producing N-( 5- substituted-1,3,4-oxadiazole-2-yl)-1-cyclopentene-1,2-dicarboxyl amic acids and N-(Substitutedbenzothiazole-2-yl)-1-cyclopentene-1,2-dicarboxyl amic acids which in turn were dehydrated in the second step via fusion method to afford he desirable N-(5-substituted-1,3,4-oxadiazole-2-yl)-1-cyclopentene-1,2-dicarboxylimides and N-(Substituted benzothiazole-2-yl)1-cyclopentene-1,2-dicarboxylimides respectively. Structures of the prepared compounds were characterized by depending on FTIR, U.V spectral data which were in agreement with the proposed ones. Finally antibacterial activity of some of the prepared new cyclic imides were studied by two types of bacteria and the results showed that the most of the tested imides posses good biological activity against these bacteria.

Microwave promoted one-pot synthesis of 2-aryl substituted 1,3,4-oxadiazoles and 1,2,4-oxadiazole derivatives using Al3+-K10 clay as a heterogeneous catalyst

An efficient, inexpensive method is developed for the one-pot synthesis of 2-aryl substituted 1,3,4-oxadiazoles and 1,2,4-oxadiazoles starting from acid hydrazides and trimethyl orthoformate under solvent-free, microwave conditions using a reusable Al3+-K10 montmorillonite clay as a heterogeneous catalyst. The novelty of the present study lies in the synthesis of oxadiazole and benzimidazole moieties in a one-pot process in high yield from easily available precursors and catalysts under mild conditions.▪

Ferroelectric phases in non-symmetric achiral bent liquid crystals towards ambient temperatures: a novel series with oxadiazol as central moiety

Extensive survey carried out in bent liquid crystals (BLCs) exhibiting ferroelectric (FE) phases suggested for the design of non-symmetric (NS) frame. Novel series of BLCs (C8Cm) with distinct lateral moieties and heterocyclic central (oxadiazole) moiety, viz., octyl 4-(5-(4´-(alkyloxy) biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzoates, are reported. NS BLC frame is realised by incorporating differing number of aromatic cores and varied length of end chains in the lateral moieties. Lateral moiety with biphenyl core is prepared by Suzuki coupling. Purity of the BLC product is confirmed by 1H NMR and elemental analysis. LC phases exhibited by C8Cm series of BLCs for m = 8, 10, 12, 15 and 16 are characterised by polarisation optical microscopy (POM), differential scanning calorimetry (DSC) and spontaneous polarisation (PS) techniques. C8Cm series are found to exhibit SmA, CrystalB, B2, B5, SmG and SmE phase variance. SmG occurs as monotropic phase. Temperature variation of PS(T) studied in FE B2 and B5 phases by field reversal method infers a moderate PS value of ~80–100 nC · cm−2. Order parameter growth in FE B2 and B5 phases is analysed through PS(T). Normalised order parameter θN exhibits asymptotic behaviour with universal temperature TU. Influence of aromatic cores and length of end chains (in lateral moieties) on the thermal stability of FE phases is discussed in the wake of the data on other BLCs.