Design, synthesis, and anticancer evaluation of novel coumarin/thiazole congeners as potential CDK2 inhibitors with molecular dynamics.

A series of novel coumarin-thiazoles was designed and synthesized as a possible CDK2 inhibitor with anticancer activity with low toxicity. The design relied on having hydrazine thiazole or its open-form thioamide to form H-bonds with the ATP binding site while coumarin maintained the crucial hydrophobic interactions for proper fitting. The biological evaluation revealed that the hydroxycoumarin-thiazole derivative 6c demonstrated the best inhibition with HepG2 and HCT116 IC50 2.6 and 3.5 µM, respectively. Similarly, its open thioamide chain congener 5c exhibited potent inhibition on MCF-7 and HepG2 with IC50 of 4.5 and 5.4 µM, respectively. Molecular docking simulations supported the assumption of inhibiting CDK2 by preserving the crucial interaction pattern with the hinge ATP site and the surrounding hydrophobic (HPO) side chains. Furthermore, molecular dynamics simulations of 5c and 6c established satisfactory stability and affinity within the CDK2 active site.

Tail-approach based design, synthesis, and cytotoxic evaluation of novel disubstituted and trisubstituted 1,3-thiazole benzenesulfonamide derivatives with suggested carbonic anhydrase IX inhibition mechanism.

A novel series of 2,4,5- and 2,3,4-trisubstituted thiazole hybrids with 1,3,4-thiadiazolylbenzenesulfonamide was designed following the tail approach as possible hCAIX inhibitors. The key intermediate 1 was condensed with thiosemicarbazide 2a to give 1,3,4-thiadiazolylthiosemicarbazone 3, which upon hetero-cyclization with substituted α-haloketones and esters afforded 2,4,5-trisubstituted thiazole-1,3,4-thiadiazole conjugates 4-8. Furthermore, the trisubstituted thiazole-1,3,4-thiadiazole hybrids 12a-d were synthesized via the regioselective cyclization of 4-substituted-1,3,4-thiadiazolylthiosemicarbazones with phenacyl bromide. The cyclized 2,4-disubstituted thiazole 4 enhanced cytotoxicity by nine, four and two times against HepG-2, Caco2, and MCF-7, respectively. Moreover, the simple methyl substitution on the thiosemicarbazone terminus 9a improved the parent derivative 3 cytotoxicity by nine, fourteen, and six times against HepG-2, Caco2, and MCF-7, respectively. This astonishing cytotoxicity was elaborated with hCAIX molecular docking simulation of 4, 9a, and 12d demonstrating binding to zinc and its catalytic His94. Furthermore, molecular dynamic simulation 9a revealed stable hydrogen bonding with hCAIX with interaction energy of -61.07 kcal mol-1 and ΔGbinding MM-PBSA of -9.6 kcal mol-1.

Recent Progress in the Development of Organic Chemosensors for Formaldehyde Detection.

Formaldehyde has become a prominent topic of interest because of its simple molecular structure, release from various compounds in the near vicinity of humans, and associated hazards. Thus, several researchers designed sophisticated instrumentations for formaldehyde detection that exhibit real-time sensing properties and are cost-effective and portable with high detection limits. On these grounds, this review is centered on an analysis of optical chemosensors for formaldehyde that specifically fall under the broad spectrum of organic probes. In this case, this review discusses different organic functionalities, including amines, imines, aromatic pillar arenes, ß-ketoesters, and ß-diketones, taking part in various reaction mechanisms ranging from aza-Cope rearrangement and Schiff base and Hanztch reactions to aldimine condensation. In addition, this review distinguishes reaction mechanisms according to photophysical phenomena, that is, aggregation-induced emission, photoinduced electron transfer, and intramolecular charge transfer. Furthermore, it addresses the instrumentation involved in gas-based and liquid formaldehyde detection. Finally, it discusses the gaps in existing technologies followed by a succinct set of recommendations for future research.

Novel asymmetrical azines appending 1,3,4-thiadiazole sulfonamide: synthesis, molecular structure analyses, in silico ADME, and cytotoxic effect.

Toward finding potential and novel anticancer agents, we designed and prepared novel differently substituted unsymmetrical azine-modified thiadiazole sulfonamide derivatives using the "combi-targeting approach". An efficient procedure for synthesizing the designed compounds starts with 5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadi-azoline 4. The E/Z configuration for compound 5 was investigated based on spectral analysis combined with quantum mechanical calculation applying the DFT-B3LYP method and 6-31G(d) basis set. The computational results found that the E isomer was energetically more favorable than the Z isomer by 2.21 kcal mol-1. Moreover, 1H and 13C chemical shifts for the E and Z isomers in DMSO were predicted using the GIAO-B3LYP/6-31G(d) computations and IEF-PCM solvation model. The computed chemical shifts for both isomers are consistent with those observed experimentally, indicating that they exist in the solution phase. Moreover, the E/Z configuration for the synthesized azines 7a-c, 9, 11, 13, 15a and 15b was also studied theoretically using the DFT-B3LYP/6-31G(d) calculations. In silico prediction for the biological activities was reported regarding the HOMO-LUMO energy gaps and molecular reactivity descriptors besides the ADMT/drug-likeness properties. The cytotoxic effect of the synthesized compounds has been assayed via the determination of their IC50.

Design, synthesis and cytotoxic evaluation of novel bis-thiazole derivatives as preferential Pim1 kinase inhibitors with in vivo and in silico study.

Bis-thiazole derivatives were synthesised conforming to the Pim1 pharmacophore model following Hantzsch condensation. Pim1 has a major role in regulating the G1/S phase which upon inhibition the cell cycle stops at its early stages. Derivatives 3b and 8b showed the best Pim1 IC50 0.32 and 0.24 µM, respectively relative to staurosporine IC50 0.36 µM. Further confirmation of 3b and 8b Pim1 inhibition was implemented by hindering the T47D cell cycle at G0/G1 and S phases where 3b showed 66.5% cells accumulation at G0/G1 phase while 8b demonstrated 26.5% cells accumulation at the S phase compared to 53.9% and 14.9% of a control group for both phases, respectively. Additional in vivo cytotoxic evaluation of 3b and 8b revealed strong antitumor activity with up-regulation of caspase-3 and down-regulation of VEGF and TNF α immune expression with concomitant elevation of malondialdehyde levels in case of 8b.

Bactericidal activity of a substituted thiazole against multidrug-resistant Eggerthia catenaformis isolated from patients with dental abscess.

Human infections caused by the anaerobic bacterium Eggerthia catenaformis are rare. However, a growing number of case reports have presented the bacterium as the causative agent in many serious complications. This study provides data on the isolation and antibiotic susceptibility profiles of E. catenaformis from dental abscess. Identification of isolates was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). We also investigated the antibacterial activity of 5-acetyl-4-methyl-2-(3-pyridyl) thiazole (AMPT) on E. catenaformis isolates. Minimum inhibitory concentrations (MICs) were determined by an agar dilution method and bactericidal activity was evaluated by a time-kill assay. Moreover, the mechanism of action of AMPT was also explored by cell membrane disruption assay and scanning electron microscopy (SEM). MALDI-TOF MS results revealed unambiguous identification of all isolates with score values between 2.120 and 2.501. Isolates NY4 and NY9 (20% of isolates) were found resistant to multiple antibiotics judged by MIC values. As multidrug-resistant strains of E. catenaformis were not reported to date, we then confirmed the identity of NY4 and NY9 based on 16S rRNA gene sequence. Favorably, all isolates were susceptible to AMPT with an MIC range of 0.25-1 mg/L. Time-kill kinetics of AMPT indicated that it exhibited potent bactericidal activity against the multidrug-resistant isolates NY4 and NY9. Furthermore, this study also hypothesizes that AMPT exerts its antibacterial effect through damaging the cell membrane and thereby induce the release of intracellular components. AMPT could therefore be considered as a therapeutic option for infections caused by multidrug-resistant bacteria.

Antibacterial and anti-quorum sensing activities of a substituted thiazole derivative against methicillin-resistant Staphylococcus aureus and other multidrug-resistant bacteria.

Management of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is still challenging. We herein report the antibacterial and anti-quorum sensing (anti-QS) activities of 5-acetyl-4-methyl-2-(3-pyridyl) thiazole (AMPT) against MRSA and other multidrug-resistant bacteria. Minimum inhibitory concentrations (MICs) were determined by agar dilution method and bactericidal activity was assessed by a time-kill assay. The anti-QS activity was evaluated using Chromobacterium violaceum. The effect of AMPT on virulence factors production by MRSA and biofilm formation by MRSA, C. violaceum and Pseudomonas aeruginosa was also assessed. AMPT was superior to vancomycin and teichoplanin against MRSA isolates. MIC50/90 values of AMPT (2/4 mg/L) were 2-4 folds lower than the values for vancomycin (4/16 mg/L) and 2-fold lower than the values for teichoplanin (4/8 mg/L). Results of time-kill assay against two multidrug-resistant MRSA isolates revealed bactericidal effect of AMPT after 4 h of treatment, with no bacterial cells detected after 24 h. Remarkably, AMPT exhibited anti-QS activity against both C. violaceum and MRSA at subinhibitory concentrations. Moreover, AMPT reduced haemolysin and protease production by MRSA and inhibited biofilm formation by MRSA, C. violaceum and P. aeruginosa but had no dispersion effect on preformed ones. Furthermore, molecular docking analysis revealed promising interactions between AMPT and AgrA as well as SarA in S. aureus confirming the antivirulence and antibiofilm activities. Favourably, no significant cytotoxicity of AMPT was observed on murine macrophage cell line. Taken altogether, these results suggest that AMPT could be considered an interesting lead compound in the search for treatment of MRSA infections.

New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors.

New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for 99mTc that showed a remarkable uptake and targeting ability towards the infection site that was induced in mice.

Mercerization effect on structure and electrical properties of cellulose: Development of a novel fast Na-ionic conductor.

Mercerized cellulose (alkali cellulose C6H10O5* NaOH) was obtained by treatment of cotton linters (cellulose) with aqueous sodium hydroxide. Cellulose and alkali-cellulose samples with relative density of 78% and 79% were obtained after sintering the material in air at optimal sintering temperatures of 423 K and 473 K, respectively. The electrical properties of the samples were studied by impedance spectroscopy in the frequency range from 13 MHz to 50 Hz at temperatures between 393 K and 493 K. The influence of cellulose mercerization on electrical properties of cotton linters was observed. The cellulose behaves like an electrical insulator. Contrariwise, the alkali-cellulose is a fast-ionic conductor with a conductivity value of σ473 K = 3.22 × 10-6 S cm-1 having activation energies of 0.49 eV and 0.68 eV at temperature range of 393 K-458 K and 459 K-500 K, respectively. The change of activation energy value has been discussed in relation to thermal stability.

Synthesis and evaluation of N-allylthiourea-modified chitosan for adsorptive removal of arsenazo III dye from aqueous solutions.

N-allylthiourea chitosan (ATUCS), a chelating material, was prepared, characterized, and studied for the removal of arsenazo III (As (III)) dye from aqueous solution. Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and 1H- and 13C-nuclear magnetic resonance (NMR) were used to characterize the prepared adsorbent and to investigate the adsorption mechanism. Furthermore, the adsorption behavior of chitosan (CS) and ATUCS were studied under various conditions. The equilibrium adsorbed amount of As (III) onto ATUCS was found to be 116.3 mg/g, compared to 87.3 mg/g with respect to CS. The regeneration of the loaded CS and ATUCS were studied using 1:1 solution of H2O2-H2SO4 and reused with certain change in efficiency after the third cycle. The adsorption process was found to fit well with pseudo-second-order kinetic model. The equilibrium data were better described with the Freundlich isotherm. The monolayer adsorption capacity was found to be 204.08 and 90.90 mg/g for the As (III)/ATUCS and As (III)/CS systems, respectively, at 25 °C. The pH of the higher uptake of As (III) onto ATUCS and CS was 4-5 and 8.0, respectively. The results demonstrated improved adsorption of As (III) using ATUCS as compared to the CS.

Novel hydrazide-hydrazone and amide substituted coumarin derivatives: Synthesis, cytotoxicity screening, microarray, radiolabeling and in vivo pharmacokinetic studies.

The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7. Moreover, 11b inhibited GST and CYP3A4 in a dose dependent manner and the induced cell death could be attributed to metabolic inhibition. Moreover, 11b microarray analysis showed significant up- and down-regulation of many genes in the treated cells related to apoptosis, cell cycle, tumor growth and suppressor genes. All of the above presents BCHHD 11b as a potent anticancer agent able to overcome drug resistance. In addition, compound 11b was able to serve as a chemical carrier for 99mTc and the in vivo biodistribution study of 99mTc-11b complex revealed a remarkable targeting ability of 99mTc into solid tumor showing that 99mTc-11b might be used as a promising radiopharmaceutical imaging agent for cancer.

Synthesis, antitumor evaluation and microarray study of some new pyrazolo[3,4-d][1,2,3]triazine derivatives.

Design and synthesis of new anticancer scaffolds; pyrazolo[3,4-d][1,2,3]triazine derivatives, is a promising solution to overcome drug resistance problem. A series of (E)-2-cyano-N-(aryl)-3-methylthio-3-(substituted-amino)acrylamides 3a-e was synthesized and transformed to the 3-aminopyrazole derivatives 4a-e which were then transformed to the target pyrazolotriazinones 6a-e. All compounds were evaluated for their anticancer activity against three different cancer cell lines namely Huh-7, Panc-1 and CCRF. Compounds 3a, 3c, 6a and 6c showed excellent anticancer activity against Huh-7 cell line (IC50: 4.93-8.84 µM vs doxorubicin 5.43 µM). Similarly, compounds 6a and 6d showed excellent activities against Panc-1 cells (IC50: 9.91 µM and 4.93 µM vs doxorubicin 6.90 µM). Caspase-Glo 3/7 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases 3/7. Microarray experiment for Huh-7 cells treated with 6c was performed to search for other molecular changes. SLC26A3, UGT1A1, UGT2B15, UGT2B7, DNASE1, MUCDH1 and UGT2B17 were among the up-regulated genes, while, GIP3, TAGL, THBS1, IFI27, FSCN1 and SOCS2 were among the most extensively down-regulated genes. These genes belong to apoptosis, metabolism, cell cycle, tumor growth and suppressor genes. Finally, pyrazolo[3,4-d][1,2,3]triazine derivatives could be potent anticancer drugs in the future.

An unexpected reactivity during periodate oxidation of chitosan and the affinity of its 2, 3-di-aldehyde toward sulfa drugs.

In an attempt to determine the reactivity during the periodate oxidation of the vicinal amino sugar, chitosan was oxidized by KIO4 in a neutral medium. The reactivity was unexpectedly found to be low. The formation of di-aldehyde chitosan (DACT) might cause the low reactivity of chitosan oxidation. Therefore, density functional theory (DFT) calculations were carried out, which revealed that the greater stability of the cyclic amino iodate intermediate might retard the ring opening to form DACT. Furthermore, the affinity of the formation of two novel Schiff bases from the interaction of delivered DACT with two sulfa drugs [sulfanilamide and sulfathiazole] was also investigated using aldehyde content estimation. DACT and Schiff's bases were characterized by FT-IR spectroscopy, X-ray diffraction, and DTA analysis. The X-ray diffraction plane (110) of DACT at the high angle side was expanded more by sulfathiazole than sulfanilamide, indicating that sulfathiazole reacted effectively with DACT. The lowest interaction of DACT with sulfa drugs could be ascribed to the lowest aldehyde content and the intramolecular hemiacetal formation that hinders the Schiff's base condensation.

Peculiar behavior of starch 2,3-dialdehyde towards sulfanilamide and sulfathiazole.

In this study, starch (1) was oxidized to starch-2,3-dialdehyde (DAS; 2) using potassium periodate. In addition, two novel Schiff's bases (5 &6) were synthesized via a condensation reaction between DAS (2) and sulfa drugs (sulfanilamide; 3 & sulfathiazole; 4). The synthesized Schiff's bases (5 &6) were characterized by FT-IR spectroscopy, X-ray diffraction and DSC analysis. DAS can easily be oxidized owing to its high aldehyde content (91.0%). However, it has low reactivity towards sulfanilamide (3) and sulfathiazole (4). According to the diffraction functional theory, this peculiar behavior is caused by the absence of V-shape in α-glucan linkage in DAS molecules, making the carbonyl group least electropositive. This reduces the nucleophilic attacks of the amino group in sulfa drugs towards the carbonyl group in DAS.

Design, synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole.

Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007 µg/mL). Moreover, compounds 7c-d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03-0.06 µg/mL and 0.06-0.12 µg/mL versus ampicillin 0.24 µg/mL and 0.12 µg/mL; respectively). Compounds 7a and 7c-d were highly potent against Escherichia coli (MIC, 0.49-0.98 µg/mL versus gentamycin 1.95 µg/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.

Physicochemical characterization of novel Schiff bases derived from developed bacterial cellulose 2,3-dialdehyde.

The synthesis of two novel Schiff's bases (cellulose-2,3-bis-[(4-methylene-amino)-benzene-sulfonamide] (5) & cellulose-2,3-bis-[(4-methylene-amino)-N-(thiazol-2-yl)-benzenesulfonamide] (6) via condensation reactions of periodate oxidized developed bacterial cellulose ODBC (2) with sulfa drugs [sulfanilamide (3) & sulfathiazole (4)] was reported. The physicochemical characterization of the condensation products was performed using FTIR, (1)H NMR, (13)C NMR spectral analyses, X-ray diffraction and DTA. The ODBC exhibited the highest degree of oxidation based on the aldehyde group number percentage (82.9%), which confirms the highest reactivity of developed bacterial cellulose [DBC (1)]. The X-ray diffractograms indicated an increase in the interplanar distance of the cellulose Schiff base (6) compared to ODBC (2) due to sulfathiazole (4) inclusion between ODBC (2) sheets corresponding to the 1 1 0 plane. In addition, the aldehyde content of Schiff base (6) was (20.8%) much lower than that of Schiff base (5) (41.5%). These results confirmed the high affinity of sulfathiazole (4) to the ODBC (2) chain, and the substantial changes in the original properties of ODBC were due to these chemical modifications rather than the sulfanilamide (3).

Design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety.

Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. In this context, new functionalized thiophene, acrylamide, arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety were designed, synthesized and evaluated for their in vitro antibacterial and antifungal activities. Among the synthesized compounds, thiophene 4d and 6-thioglucosylpyridone 17 displayed significant antibacterial activities against Escherichia coli (MIC, 0.007 µg/mL vs gentamycin 1.95 µg/mL) and Bacillis subtilis (MIC, 0.007 µg/mL vs ampicillin 0.24 µg/mL), respectively. Whereas, the pyrazole 6 showed the highest antifungal activity against Aspergillus fumigates (MIC, 0.03 µg/mL vs amphotericin B 0.12 µg/mL). In general, most of the synthesized compounds exhibited better antimicrobial activities than sulfisoxazole; this might be attributed to the synergistic effect of the sulfonamide and attached heterocyclic moieties as well as the increased lipophilic characters of the synthesized compounds. Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of microbial DHPS enzyme. The results provide important information for the future design of more potent antimicrobial agents.

Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives.

Drug resistance is a major impediment for cancer treatment, to overcome it we designed and synthesized sixteen coumarins bearing hydrazide-hydrazone moiety and evaluated them against human drug-resistant pancreatic carcinoma (Panc-1) cells and drug-sensitive (hepatic carcinoma; Hep-G2 and leukemia; CCRF) cell lines in vitro. The 6-brominated coumarin hydrazide-hydrazone derivatives (BCHHD) 7c, 8c and 10c were more potent than doxorubicin (DOX) against resistant Panc-1 cells. BCHHD 7c showed significant cytotoxicity against all tested cells (IC50: 3.60-6.50 µM) on comparison with all other coumarin hydrazide-hydrazone derivatives (CHHD), whereas BCHHD's 8c and 10c showed significant antiproliferative activity only against resistant Panc-1 cells with IC50 of 2.02 µM and 2.15 µM, respectively. All the investigated BCHHD's were able to activate caspases 3/7 and they could induce apoptosis in resistant Panc-1 cells. Microarray analysis showed that BCHHD 7c induced the expression of apoptotic- and cell cycle arrest (G2/M)- genes in resistant Panc-1 cells. Moreover, BCHHD 7c induced the up-regulation of CDKN1A, DDIT4, GDF-15 and down-regulation of CDC2, CDC20, CDK2 genes. Based on our results, we conclude that 7c could be a potent anticancer drug to overcome drug resistance in cancer and it could be highly beneficial for patients in the clinic.

Synthesis of some new 2-(3-pyridyl)-4,5-disubstituted thiazoles as potent antimicrobial agents.

As a part of ongoing studies in developing new potent antimicrobial agents, a series of novel 2-(3-pyridyl)-4,5-disubstituted thiazoles was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disc diffusion assay. Among the synthesized compounds, 5-acetyl-4-methyl-2-(3-pyridyl)thiazole (5) exhibited twofold antibacterial activity of ampicillin in inhibiting the growth of Staphylococcus epidermidis (MIC 0.24 µg/mL) and also showed equipotent antifungal activity with amphotricin B against Geotricum candidum (MIC 0.48 µg/mL). From structure-activity relationship (SAR) point of view, increasing the size of the substitutions either at position 4 or 5 on the thiazole nucleus decreased the antimicrobial activity.

Synthesis and antitumor evaluation of some new 1,3,4-oxadiazole-based heterocycles.

The synthetic strategies and characterization of some novel 1,3,4-oxadiazole derivatives carrying different pharmacophores and heterocyclic rings that are relevant to potential antitumor and cytotoxic activities are described. The antitumor activities of the newly synthesized compounds were evaluated according to the protocol of the National Cancer Institute (NCI) in-vitro disease-oriented human cells screening panel assay. The results revealed that five compounds, namely 2, 7a, 11a, 12b, and 17; displayed promising in-vitro antitumor activity in the 4-cell lines assay. Incorporating a thiazole ring to 1,3,4-oxadiazole skeleton resulted in better antitumor activities than those displayed by the pyrazole and thiophene ring systems. Transformation of 1,3,4-oxadiazole 2 to N-(6-amino-7H-pyrazolo[5,1-c][1,2,4]triazol-3-yl)benzamide (15) diminished the antitumor activity.