Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents

Abstract

New N-(5-methyl-4-phenylthiazol-2-yl)-2-(substituted thio)acetamides were synthesized and studied for their anticancer activity. The title compounds were procured by reacting 2-chloro-N-(5-methyl-4-phenylthiazol-2-yl)acetamide with some mercapto derivatives. The structural elucidation of the compounds was performed by ¹H-NMR, ¹³C-NMR and LC-MS/MS spectral data and elemental analyses. The synthesized compounds were investigated for their antitumor activities against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell line for determining their selective cytotoxicity. 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenylthiazol-2-yl)acetamide (4c) showed high selectivity, and whose IC₅₀ value was determined as 23.30?±?0.35?µM and >1000?µM against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell lines, respectively. 2-[(1-Methyl-1H-imidazol-2-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4a) and 2-[(1-Methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4c) exhibited the highest apoptosis percentage among those tested, but not as high as the standard, cisplatin.     

Synthesis and biological activities of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety

A series of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety were designed, synthesized and evaluated for their antibacterial, antifungal and antiviral activities. The bioassay results indicated that most of target compounds showed good antiviral activities against tobacco mosaic virus (TMV) and antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). Especially, the anti-Xoo effect of title compounds 5k (N-(5-methoxybenzo[d]thiazol-2-yl)-2-((5-(2-tolyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) and the anti-Rs effect of title compounds 5a (N-(5-nitrobenzo[d]thiazol-2-yl)-2-((5-(4-(trifluorom ethyl)phenyl)-1,3,4-thiadiazol-2-yl)thio)acetmide) respectively reached 52.4% and 71.6% at 100?µg/mL, which are superior to that of bismerthiazol (32.0% and 52.3%). In addition, the protective and inactivation activities of title compound 5i (N-(5-methoxybenzo [d]thiazol-2-yl)-2-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) against TMV were 79.5% and 88.3%, respectively, which are better than that of ningnanmycin (76.4% and 86.8%). The above research showed that benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety may be used as potential molecular templates in searching for highly-efficient antiviral and antibacterial agents.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.     

Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

Novel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K_i values in the range of 18.90?±?2.37 ?58.25?±?13.62?nM for hCA II and 5.72?±?0.98 ?37.67?±?5.54?nM for hCA I. Also, the K_i parameters of these compounds for AChE were obtained in the range of 25.47?±?11.11???255.74?±?82.20?nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K_i value of 70.55?±?12.30?nM against hCA II, and 67.17?±?9.1?nM against hCA I, and tacrine inhibited AChE showed K_i value of 263.67?±?91.95.     

Synthesis of novel pyrimidine derivatives with (pyridin-3-ylmethyl)thio and phenylamino moieties and evaluation of their antifungal activity

A series of novel pyrimidine derivatives with (pyridin-3-ylmethyl)thio and phenylamino moieties were synthesized from ethyl acetoacetate, thiourea, 3-pyridinylmethyl chloride hydrochloride, and substituted anilines by multi-step reactions. The structures of the target compounds were characterized by IR, ¹H NMR, ¹³C NMR and elemental analysis. The in vitro antifungal activities against Botrytis cinerea and Sclerotinia sclerotiorum were evaluated. The result showed that N-phenyl-6-methyl-2- ((pyridin-3-ylmethyl)thio) pyrimidin-4-amine (4a) displayed high inhibition activity against Botrytis cinerea with 87.5%inhibition at 100 µg/mL; 4a, and N-(4-isopropylphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4c), N-(4-methoxyphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4d) and N-(2-hydroxy-5-chloro)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin- 4-amine (4h) exhibited sufficient activities against Sclerotinia sclerotiorum with 86.6% –93.7% inhibitions at the same concentration.     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita

Abstract

A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0?mg L^?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0?mg L^?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.     

2-(Benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidates: Synthesis,characterization and antimicrobial activity evaluation

A series of new 2-(benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidate derivatives (7a-j) of biological interest are synthesized in two steps via an in situ process without the isolation of the intermediate. 2-(Benzo[d]thiazol-2-yl) phenol (3) was treated with 4-nitrophenyl phosphorodichloridate(4) to obtain the monochloro intermediate, 2-(benzo[d]thiazol-2-yl)phenyl (4-nitrophenyl) phosphorochloridate(5). It was subsequently reacted with various amines, 6(a-j) to afford the desired title products. IR, NMR (¹H, ¹³C and ³¹P), mass spectral and elemental analysis are used to characterize the structures of the newly synthesized compounds. The antibacterial and antifungal activities are determined by the growth of inhibition of bacteria and fungi of the title compounds at two concentrations, 50 and 100 µg/mL, and minimum inhibitory concentrations to the active compounds. The compounds 7e, 7f and 7j exhibited promising inhibition activity against bacterial strains and 7c, 7e and 7i against A. niger and C. albicans and MIC values are in the range of 10.0–15.0 µg/mL.     

Nano silver particles catalyzed synthesis,molecular docking and bioactivity of α-thiazolyl aminomethylene bisphosphonates

Abstract

A new series of α-thiazolyl aminomethylene bisphosphonates were synthesized by a three component reaction of 4-aryl substituted thiazol-2-amine with different dialkyl/aryl phosphites and triethyl orthoformate in the presence of Ag NPs (nano particles) as a catalyst under solvent free conditions. All the synthesized target compounds were characterized by ¹H, ¹³C, ³¹P, mass and elemental analysis. The target compounds were screened for their in vitro antioxidant, antibacterial and antifungal activity. Molecular docking studies were also performed. The results revealed that among the synthesized compounds tetramethyl(((4-(4-methoxyphenyl)thiazol-2-yl)amino) methylene)bis(phosphonate) (5d), tetramethyl(((4-(4-fluorophenyl)thiazol-2-yl)amino) methylene) bis(phosphonate) (5h), and tetramethyl(((4-(4-bromophenyl)thiazol-2-yl)amino)methylene) bis (phosphonate) (5j) showed remarkably higher antioxidant activity by DPPH and H₂O₂ than the standard ascorbic acid. Compounds tetramethyl(((4-phenyl thiazol-2-yl)amino) methylene) bis(phosphonate) (5a), 5d, 5h and tetraethyl(((4-(4-bromophenyl)thiazol-2-yl) amino)methylene)bis (phosphonate) (5k) showed good antibacterial activity. 5a, 5d, and 5h also showed rather higher antifungal activity than the standard flucanozole. Computational docking methods have been used to predict how several aminomethylene bisphosphonate derivatives compete against the inhibitor BPH-1330 at the crystal enzyme structure of the 4H3A protein active site and how R and R₁ influence their binding ability.     

Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity against pine-wood nematodes

Abstract

To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives containing a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities. The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most of the title compounds displayed nematicidal activity at a concentration of 40?mg/L. Especially, the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e), 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo [3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against Bursaphelenchus xylophilus.     

Synthesis,structures, catalytic,and anticancer activities of some coordination compounds involving two new triazole derivatives

Five N-heterocyclic carboxylate-based coordination complexes, [Co(L¹)₂(H₂O)₂]·2H₂O (1), [Cd(L¹)₂(H₂O)₂]·2H₂O (2), [Co(L²)(H₂O)₃] (3), [Ni(L²)(H₂O)₃] (4), and [Cu₂(L²)₂(H₂O)₂] (5), have been synthesized and characterized by elemental analysis, IR spectroscopy, Powder X-ray diffraction, thermogravimetric analyses, and single-crystal X-ray crystallography, where HL¹ is 2-((5-amino-1H-1,2,4-triazol-3-yl)thio)acetic acid and H₂L² is 2-((5-amino-1-(carboxymethyl)-1H-1,2,4-triazol-3-yl)thio)acetic acid. In these complexes, the hydrogen bonds (H-bonds) play an important role in their packing structures. Complex 1 has nine H-bonds showing a 3-D sqc38 topology. Complex 2 has 17 H-bonds exhibiting a 3-D hxl network. Complexes 3 and 4 are isomorphic, both of which possess ten H-bonds to present a 3-D btc topology. Complex 5 with eight H-bonds forms a 2-D sq1 structure. In addition, complex 3 catalyzes the decolorization of methyl orange. Meanwhile, 1, 3, and 5 show certain anticancer activities to inhibit the growth of HepG2 cells.     

Chemical constituents and cytotoxic activity from the wood-decaying fungus Xylaria sp. SWUF08-37

Abstract

A new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3–15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey’s method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC₅₀?=?19.60?µg/mL), HT29 (IC₅₀?=?17.31?µg/mL), HCT116 (IC₅₀?=?14.28?µg/mL), MCF-7 (IC₅₀?=?15.38?µg/mL), and Vero (IC₅₀?=?24.97?µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines.     

Synthesis of some novel 3,4,5-trisubstituted triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity

Abstract

Some new 3,4,5-trisubstituted 1,2,4-triazole derivatives were synthesized and studied for their antimicrobial activity. The lead compounds were obtained starting from 8-hydroxyquinoline and ethyl 2-chloroacetate. The obtained ester compound (1) first reacted with hydrazine hydrate (2) then with phenyl isothiocyanate (3). Ring closure by KOH led to 3-mercapto-1,2,4-triazole derivative (4). Lastly, it reacted with 2-chloro-N-(substituted (benzo)/thiazole)acetamide derivatives to obtain the final compounds (5a–j). The structural elucidation of the compounds was performed by ¹H NMR and ¹³C NMR spectroscopy and high resolution mass spectrometry techniques and elemental analysis. The synthesized compounds were investigated for their antimicrobial activities against seven bacteria and four fungi. As a result of the activity studies, it was observed that compounds N-(6-nitrobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5a) and N-(6-fluorobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5d) were the most active molecules. Also, the antifungal activity of the compounds was found to be higher than their antibacterial activity although lower than the standard drug’s potential. Additionally, the physicochemical properties of the compounds were calculated which were evaluated to be at a suitable range for oral administration.     

Electrochemical Determination of the KRAS Genetic Marker for Colon Cancer with Modified Graphete and Graphene Paste Electrodes

The determination of KRAS was performed using electrochemical sensing devices based on graphite and graphene pastes, modified with a phthalocyanine-boron dipyrromethene (BODIPY) and azulenes dyes. The limits of quantification for KRAS were 1.54?×?10^?4?µg/mL using the sensor based on the phthalocyanine-BODIPY dye and graphite, 2.64?×?10^?7?µg/mL using the sensor based on 2,6-bis((E)-2-(furan-2-yl)vinyl)-4-(4,6,8-trimethylazulen-1-yl)pyridine/TiO₂Pt/reduced graphene oxide, and 3.84?×?10^?3?µg/mL using the sensor based on 2,6-bis((E)-2-(thiophen-3-yl)vinyl)-4-(4,6,8-trimethylazulen-1-yl)pyridine/TiO₂Pt/reduced graphene oxide. Recovery measurements demonstrated the suitable analytical performance of these sensors for the early detection of colon cancer by the analysis of whole blood samples.     

Tagetnoic acid,a new lipoxygenase inhibitor peroxy fatty acid from Tagetes minuta growing in Saudi Arabia

Abstract

A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were separated from the n-hexane fraction of the aerial parts of Tagetes minuta L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds 3–5 displayed potent lipoxygenase inhibitory potential with IC₅₀s 2.26, 1.83, and 1.17?μM, respectively compared to indomethacin (IC₅₀ 0.89?μM). Moreover, molecular docking study revealed that the potent activity of 5 is due to H-bonding and hydrophobic interaction. The results of this study suggested that Tagetes minuta dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.     

One-pot synthesis of novel 1,2,3-triazole-pyrimido[4,5-c]isoquinoline hybrids and evaluation of their antioxidant activity

A series of novel pyrimido[4,5-c]isoquinolines (3a–3h) and 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinolines (4a–4h) were synthesized in good to excellent yields in the one-pot method. The reaction of 6-amino-1,3-dimethyluracil with different 2-iodo benzoyl chlorides using Pd catalyst in dimethylformamide afforded corresponding pyrimido[4,5-c]isoquinolines (3a–3h). One-pot reaction of pyrimido[4,5-c]isoquinolines with propargyl bromide and benzyl azide in THF at room temperature furnished 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinoline (4a–4h). In vitro antioxidant activity examination revealed that compounds 4d and 4c found to exhibit potent antioxidant activity as compared to the standard drug Trolox with IC₅₀ values 6.02?±?0.6 and 12.18?±?0.9?µM, respectively.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Synthesis and antimicrobial activity of new 2-((1-furan-2-yl)ethylidene)hydrazono)-4-phenylthiazol-3(2H)-amine derivatives and their schiff bases with 4-nitrobenzaldehyde

Abstract

A new series of 2-((1-furan-2-yl)ethylidene)hydrazono)-4-substitutedphenylthiazol-3(2H)-amines (2a–2o) and their Schiff bases (3a–3o) from 4-nitrobenzaldehyde were synthesized. The chemical structures of all the synthesized compounds were confirmed by their IR, ¹H-NMR, ¹³C-NMR spectroscopy and mass spectrometry. They were screened for their antimicrobial and antifungal activities. Additionally, in vitro cytotoxic acivity of the most active antifungal compound (3o) and ketoconazole was determined in NIH/3T3 cells by MTT assay. Compound 2i (4-{3-Amino-2-[(1-(furan-2-yl)ethylidene)hydrazono]-2,3-dihydrothiazol-4-yl}phenol) showed the greatest antifungal activity among the newly synthesized derivatives. Schiff bases (3c-3n) displayed an undeniable fungicidal action against Candida parapsilosis ATCC 22019 as intense as the reference ketoconazole. In addition, the most active Schiff base 3o (2-[(1-(Furan-2-yl)ethylidene)hydrazono]-N-(4-nitrobenzylidene)-4-(2,3,4-trichloro phenyl)thiazol-3(2H)-amine) showed the highest antifungal activity against both Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019, and was as potent as ketoconazole. Moreover, compound 3o was found to be non-cytotoxic against NIH/3T3 cells.     

Synthesis and biological evaluation of 1,2,4-oxadiazole linked 1,3,4-oxadiazole derivatives as tubulin binding agents

As an aspect of our ongoing research in search of new anticancer agents, a series of novel analogs of 1,3,4-oxadiazole embedded with 1,2,4-oxadiazole moieties (11a–j) were synthesized. The structure of the final compounds was confirmed by ¹H NMR, ¹³CNMR and mass spectroscopic techniques and evaluated for their in vitro anticancer activity against three human cancer cell lines (lung, breast). Among the synthesized compounds, 11?b, 11?g, 11?h, and 11i showed potent anticancer activity with IC₅₀ values within the range of 0.34?±?0.025 to 2.45?±?0.23?μM against three human cancer cell lines. Further, these compounds (11a–j) were investigated for molecular docking studies. Among them, compound 11?h showed strong binding affinity on binding sites of target protein EGFR (PDB ID: 4hjo) with highest docking score (-7.028). It revealed that 11?h was a strong tubulin binding agent.     

Facile synthesis of highly functionalized novel pyrazolopyridones using oxoketene dithioacetal and their anti-HIV activity

A series of novel 3-amino-4,5-dihydro-6-methyl-4-oxo-N-aryl-1H-pyrazolo[4,3-c]pyridine-7-carboxamide have been synthesized starting from various oxoketene dithioacetals. The cyclocondensation reaction of 2-(bis(methylthio)methylene)-3-oxo-N-arylbutanamide 2a–w with cyanoacetamide using NaOiPr as base under reflux condition afforded novel highly functionalized pyridone 3a–w derivatives. Further, [3?+?2] cyclocondensation reaction of pyridones with hydrazine in the presence of alcohol was yielded pyrazolopyridones (23 nos) 4a–w with excellent yields. All newly synthesized compounds were evaluated for in vitro anti-HIV activity using MTT method. Most of these compounds have showed moderate to potent activity against HIV-1 (III_B) and HIV-2 (ROD) strains with an IC₅₀ ranging from >18 IC₅₀[µg/ml] to <100 IC₅₀[µg/ml]. Among them, compounds 4j and 4v were identified as the most promising compound for both types of HIV strains. (IC₅₀?=?18?µg/ml). Three compounds 4l, 4m, and 4p have been found potent anti-HIV 1 and 2 activity against MT-4 cells.     

A 2-D tetrazole-based Zn(II) coordination polymer: crystal structure,dielectric constant,and luminescence

A tetrazole-based Zn(II) coordination polymer, [Zn(TMPT)₂] _n (1) (TMPT?=?5-(4-((1H-1,2,4-triazol-1-yl)methyl)phenyl)-2H-tetrazole), was synthesized by in situ reaction of 4-((1H-1,2,4-triazol-1-yl)methyl)benzonitrile, Zn(NO₃)_2?·?6H₂O, and NaN₃ under hydrothermal conditions and structurally characterized by single-crystal X-ray diffraction. Complex 1 contains π–π stacking interactions between tetrazole rings and phenyl rings of the 2-D ordered layered structural framework, which contribute to the dielectric response. In addition, 1 was demonstrated to display strong blue fluorescence emissions in the solid state at room temperature.