DNA-binding and cleavage, cytotoxicity properties of Ru(II) complexes with 2-(4′-chloro-phenyl) imidazo[4,5-f][1,10]phenanthroline, ligand and their “light switch” on–off effect

Three new complexes of the type [Ru(phen)₂PIP-Cl](1) [Ru(bpy)₂PIP-Cl](2) and [Ru(dmp)₂PIP-Cl](3) (phen = 1,10-phenanthroline; bpy = 2,2′-bipyridine; dmb = 4,4-dimethyl-2,2′-bipyridine), PIP-Cl = 2-(4′-chloro-phenyl) imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by using UV–VIS, IR and ¹H-NMR, ¹³C-NMR spectral methods. Absorption spectroscopy, emission spectroscopy, viscosity measurements and DNA melting techniques were used to investigate the binding of these Ru(II) complexes with calf thymus DNA, and photocleavage studies were used to investigate the binding of these complexes with plasmid DNA. The spectroscopic studies together with viscosity measurements and DNA melting studies supported fact that Ru(II) complexes bind to CT-DNA(calf thymus DNA) by an intercalation mode via PIP-Cl into the base pairs of DNA. Upon irradiation, these novel Ru(II) complexes cleave the plasmid pBR 322 DNA from the supercoiled form I to the open circular form II.     

Synthesis,characterization, DNA interaction,and antitumor activities of mixed-ligand metal complexes of kaempferol and 1,10-phenanthroline/2,2′-bipyridine

Four novel mixed-ligand metal complexes with the composition [Cu(Kae)(phen)]Cl·2H₂O (1), [Cu(Kae)(bpy)]Cl·H₂O (2), [Zn(Kae)(phen)]Cl·H₂O (3), and [Zn(Kae)(bpy)]Cl·H₂O (4), where Kae = kaempferol, phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine were synthesized and characterized by elemental analysis, IR, UV, ¹H NMR, ¹³C NMR, HRMS ,and molar conductivity. The binding and cleavage abilities of complexes 1–4 with DNA have been studied by fluorescence spectroscopy, viscosity measurements, and gel electrophoresis under physiological conditions. The experimental results indicated that four complexes could bind to CT-DNA via an intercalative mode, and the complex 1 showed the strongest activity to cleavage DNA (pUC 19). The in vitro cytotoxicities of kaempferol and complexes 1–4 were also evaluated against human breast carcinoma cells by MTT assays. The results show that the cytotoxicities of complexes 1–4 are much higher than that of kaempferol alone, and the complex 1 shows the strongest ability to inhibit the growth of human breast carcinoma cells. The results suggest that the complex 1 may be a valuable tool in cancer chemotherapy agents.     

Novel heteroleptic complexes of titanium(IV) derived from 2-hydroxyacetophenone: synthesis, characterization, antibacterial and molecular docking studies

A few new and versatile complexes of titanium(IV) derived from 2-hydroxyacetophenone of the types {[(Ap)Ti(OPr ⁱ )_2?n (L₂) _n ] (2a, 2e and 2f)}, {[(Ap)Ti(L₁OR)(L₂)] (2b–2d, 2g–2i)} have been synthesized by the reaction of the precursor [(Ap)Ti(OPr ⁱ )₂] with different 2-heteroaryl methyl ketone oximes and alkoxyalkanols in various molar ratios in refluxing toluene yielded mono nuclear heteroleptic derivatives, {where, n = 1–2, HAp = 2-hydroxyacetophenone, Pr ⁱ  = isopropyl, L₁ = O–CH₂–CH₂?, R = CH₃, C₂H₅, C₄H₉ and HL₂=HONC(Me)py-2, HONC(Me)fu-2}. All these newly synthesized complexes were characterized by elemental analysis, mass, UV, FT-IR and NMR (¹H, ¹³C) spectral studies. The mass spectra of the newly synthesized molecules indicate their monomeric state. Spectral studies suggest the bonding between metal and ligands in a tetra coordinated fashion. Thermogravimetric analyses indicate the multistep decomposition of complexes resulting TiO₂ as the end product at 600 °C. Antibacterial activities of these complexes were also exercised. Complex 2e is equipotent to the standard drug against Pseudomonas aeruginosa and Escherichia coli. A keen molecular docking study revealed lesser docking scores of some of these complexes than that of the standard drug gentamicin.     

Coumarin-containing aminophosphonates bridged with chiral side chain: synthesis and influence of chirality on cytotoxicity and DNA binding

A series of novel coumarin-containing α-aminophosphonates with two chiral centers were synthesized and a single-crystal structure of compound 8g (8g′, (R)-diethyl ((S)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)propanamido)(2-bromophenyl)methylphosphonate) was obtained. The in vitro antitumor activities of compound 8a–8g′ against human pulmonary carcinoma cell line (A549), human nasopharyngeal carcinoma (human KB), and human lung adenocarcinoma (MGC-803) cell lines were evaluated. Some compounds showed relatively high cytotoxicity. Compared with 8g, 8g′ exhibited an improved activity against three tumor cells, which was evidenced by the IC₅₀ that was four- to five-fold lower than those for 8g. The influence of chirality was also observed in DNA-binding assay of 8g and 8g′. 8g′ exhibited higher binding constant (1.96 × 10³ M^?1) as compared to 8g (1.69 × 10³ M^?1).     

Synthesis,antimicrobial, and antioxidant activity of benzofuran barbitone and benzofuran thiobarbitone derivatives

The synthesis of novel series of benzofuran derivatives, containing barbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl) methylidene]pyrimidin-2,4,6(1H,3H,5H)-trione (4a–i) and thiobarbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl)methylidene]-2-thioxodihydropyrimidin-4,6(1H, 5H)-dione (5a–i) have been reported. The target compounds (4a–i) and (5a–i) were synthesized by the Knoevenagel condensation of (5-substituted-1-benzofuran-2-yl)(2/4-substitutedphenyl) methanone (3a–i) with barbituric acid and thiobarbituric acid, respectively, in acid medium. These compounds were screened for the antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 4a, 5a, 4c, and 5c displayed good antibacterial and antifungal activity against all tested strains. Further, the synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate synthase and the compounds 4c and 5c have emerged has an active antimicrobial agent with least binding energy (?5.27 and ?4.85 kJ mol^?1). Compounds 4e, 4f, 5e, and 5f showed promising free radical scavenging activity and compounds 5a and 5b showed good chelating ability with Fe²⁺ ions.     

Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity

A new series of quinazoline analogs was designed, synthesized, and evaluated for their anticonvulsant activity. Compounds 6, 12, 21, 36, 37, and 38 showed 70–100 % protection against PTZ-induced seizures acting as GABA_A receptor agonists. Compound N-(3,4,5,6-tetrachloro-phthalimido)-2-[(3-phenyl-4-oxo-6-methyl-3H-quinazolin-2-yl)-thio]acetamide (12) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4H)-yl]-isoindoline-1,3-dione (38) representing the remarkably active compounds in this stud, showed ED₅₀ values of 457 and 251 mg/kg; TD₅₀ values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD₅₀ values of 1,288 and 1,380 mg/kg, and TI values of 2.82 and 5.50, respectively. Compound 38 proved to be almost twofold more active than the standard drug sodium valproate.     

Pyridine-2,5-dicarboxylate complexes with 2,2′-bipyridine and Co(II), Zn(II), Cu(II): syntheses, characterization, antimicrobial, and cytotoxic effects

In this study, three novel mononuclear M(II)-pyridine-2,5-dicarboxylate (M = Co(II), Cu(II), and Zn(II)) complexes with pyridine-2,5-dicarboxylic acid or (isocinchomeronic acid, H₂pydc) and 2,2′-bipyridine (bipy), [Co(pydc)(bipy)₂]·5H₂O (1), [Cu(pydc)(bipy)₂]·6H₂O (3), and [Zn(pydc)(bipy)₂]·6H₂O (4) have been synthesized. Elemental, thermal, and mass analysis; magnetic susceptibilities; molar conductance; IR and UV/vis spectroscopic studies have been performed to characterize the complexes. Subsequently, the results of antimicrobial activity of the two ligands H₂pydc and bipy, and the four compounds (1), (2), (3), and (4) were obtained by the agar disk diffusion method. Furthermore, the cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay for 24 and 48 h on rat glioma cells (C6).     

Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline

The practice of medicinal chemistry is devoted to the discovery and development of new agents for treating disease. A new derivative of methyl 2-((E)-3-(3,4-dihydroxyphenyl)acrylamido)benzoate 2 was synthesized by reacting the amino group of methyl anthranilate 1 with caffeic acid in the presence of PCl₃. Cyclcondensation of 2 with hydrazine hydrate afforded the corresponding 2,3-dihydro-2-(3,4-dihydroxyphenyl) pyrazolo[5,1-b]quinazolin-9(1H)-one 3. The median lethal doses (LD_50s) of compounds 2 and 3 in mice were 1,135 and 495 mg/kg b.w., respectively. The anti-inflammatory, reducing power, chelating activity on Fe²⁺, free radical-scavenging, and total antioxidant activities were more pronounced in compound 2 compared to compound 3. On the other hand, antipyretic activity was more pronounced in compound 3 compared to compound 2. Antioxidant activity of compounds 2 and 3 increased with increased concentrations. Total antioxidant activity of compounds 2, 3 and both standards decreased in the order of α-tocopherol > compound 2 > trolox > BHA > BHT > compound 3. Administration of compounds 2 and 3 orally to the rats at dose of 50, 100, and 150 mg/kg b.w., for 10 days showed non-significant changes in serum level of GOT, GPT, ALP, γ-GT, and LDH as compared with the control group. In addition, oral administration of the compound 2 at a concentration of 100 and 150 mg/kg b.w. and compound 3 at a concentration of 150 mg/kg b.w. daily to normal rats for 10 days showed a significant increase in liver GSH, GPx, GR, and GST activities and significant decrease in TBARS level. But, administration of diclofenac sodium (30 mg/kg b.w.) orally to the rats daily for 10 days to rats showed significant increase in serum SGOT, SGPT, ALP, γ-GT, and LDH and significant decrease in liver GSH, GPx, GR, and GST activities. These findings suggest that compounds 2 and 3 exhibited good antioxidant and anti-inflammatory activity and also showed effects on liver enzymes.     

Design, synthesis, molecular docking, and biological evaluation of N-methyl-3-nitro-4-(nitromethyl)-4H-chromen-2-amine derivatives as potential anti-cancer agents

A series of N-methyl-3-nitro-4-(nitromethyl)-4H-chromen-2-amine derivatives 8 were synthesized from 2-((E)-2-nitrovinyl)phenol 7 and ((E)-N-methyl)-1-(methylthio)-2-nitroethenamine 5. The cytotoxic activity of these molecules was tested against two cancer cell lines namely HeLa (cervical cancer) and HEp-2 (epidermoid laryngeal carcinoma). Among them, two molecules (4H-chromenes 8h and 8i) displayed potent anti-proliferative activity with IC₅₀ values of 115.04 and 18.96 μM for HeLa and 86.94 and 25.08 μM for Hep-2 cell lines, respectively. Morphological evaluation of the cell lines revealed that both 8h and 8i induce the apoptotic process. Molecular docking studies of all the 4H-chromenes 8 with anti-apoptotic Bcl-2, Bcl-w, and Bcl-xL proteins revealed that the 4H-chromenes 8h and 8i have good docking score and thus corroborated in vitro studies. Furthermore, evaluation of Lipinski and ADMET properties revealed their drug-like pharmacokinetic profiles. Thus, 4H-chromenes 8h and 8i exhibit promising anti-cancer properties and can be used as lead compounds for further development.     

Design, synthesis and in vitro antimicrobial activity of novel phenylbenzamido-aminothiazole-based azasterol mimics

Phenylbenzamide framework as a mimic of the azasterol structure was investigated by synthesizing 4-phenylbenzamido-2-aminothiazole 4, and evaluating its MIC against Escherichia coli, Enterobacter cloacae, Bacillus licheniformis and Mycobacterium tuberculosis (MTB) H₃₇Rv as well as antifungal activity against three test phytopathogenic fungi. Further, the bioisosterism strategy was implemented to synthesize a series of azo-derivatives of 4 (6a–6j). All the azo-compounds were screened for their antibacterial and antifungal activity. The electronic (UV–vis) absorption characteristics of the final compounds were examined. Resazurin-mediated microtitre plate-antibacterial assay was implemented for first time on these azo-derivatives. Compounds 4 and 6b had significant antibacterial activity. For the compound 4, MIC against Escherichia coli is 7.8 × 10^?3 mg/mL and MIC against Mycobacterium tuberculosis (MTB) H₃₇Rv is 16 μg/mL were identified. Compounds 4, 6d, 6g and 6h showed excellent antifungal activity, when compared to the standard nistatin, against three test phytopathogenic fungi.     

Schiff’s base derivatives bearing 2-thiophenoxyquinoline nucleus as new antibacterial agents

A series of new Schiff’s base derivatives 4a–x bearing 2-thiophenoxyquinoline nucleus have been designed and synthesized by reaction of 2-thiophenoxyquinoline-3-carbaldehydes 2a–d with various benzohydrazides 3a–f in the presence of Ni(NO₃)₂·6H₂O as a catalyst. In vitro antibacterial screening was carried out against two Gram-positive bacteria (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacteria (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525). Of the compounds studied, compound 4e showed chief activity (MIC = 3.13 μg/mL) against S. aureus, and compounds 4p, 4k, and 4w were found to possess effective antibacterial activity against employed strains compared with standards used. The structures of Schiff’s base derivatives were established by using various spectroscopic methods. A crystal structure of compound 4k has been determined by X-ray diffraction analysis.     

Acylated phenylethanoid glycosides,echinacoside and acteoside from Cistanche tubulosa,improve glucose tolerance in mice

Acylated phenylethanoid glycosides, echinacoside (1) and acteoside (2), principal constituents in stems of Cistanche tubulosa (Orobanchaceae), inhibited the increase in postprandial blood glucose levels in starch-loaded mice at doses of 250–500 mg/kg p.o. These compounds (1 and 2) also significantly improved glucose tolerance in starch-loaded mice after 2 weeks of continuous administration at doses of 125 and/or 250 mg/kg/day p.o. without producing significant changes in body weight or food intake. In addition, several constituents from C. tubulosa, including 1 (IC₅₀ = 3.1 μM), 2 (1.2 μM), isoacteoside (3, 4.6 μM), 2′-acetylacteoside (4, 0.071 μM), tubulosides A (5, 8.8 μM) and B (9, 4.0 μM), syringalide A 3-O-α-l-rhamnopyranoside (10, 1.1 μM), campneoside I (13, 0.53 μM), and kankanoside J₁ (14, 9.3 μM), demonstrated potent rat lens aldose reductase inhibitory activity. In particular, the potency of compound 4 was similar to that of epalrestat (0.072 μM), a clinical aldose reductase inhibitor.     

Synthesis and biological activity of novel Schiff bases derived from metronidazole

A number of novel Schiff bases (5a–i) and (7a–d) derived from metronidazole were synthesized. Reaction of 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester toluene-4-sulfonate with 4-hydroxybenzaldehyde and with 3-hydroxybenzaldehyde in the presence of a base afforded 4-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzaldehyde (5) and 3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzaldehyde (7), respectively. The reaction of aldehydes 5 and 7 with a number of primary aromatic amines produced Schiff bases 5a–i and 7a–d, respectively. Structures of these compounds were confirmed through different spectroscopic methods such as ¹H-NMR, ¹³C-NMR, mass spectrometry, and also by elemental analyses. The prepared compounds were evaluated in vitro for their antigiardial, anti-trichomonal, antibacterial, and antifungal activities. Compounds 5e, 5g, 5i, 7a, 7b, 7c, and 7d exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC₅₀ of 7.2, 3.3, 1.5, 5.8, 4.5, 2.9, and 3.8 µg/mL, respectively. Compounds 5a and 5c also exhibited antigiradial activity with similar IC₅₀ values compared to the reference drug metronidazole with IC₅₀ of 7.2 µg/mL. The other compounds 5b, 5d, 5f, and 5 h also showed antigiardial activity but with higher IC₅₀ compared to the reference drug. Compounds were also tested for their anti-trichomonal activity, they, however, exhibited higher IC₅₀ compared to the reference drug metronidazole (7.4 µg/mL), except for compound 5a which exhibited anti-trichomonal activity with an IC₅₀ of 6.3 µg/mL. On the bases of preliminary screening, the newly synthesized compounds exhibited moderate to potent antimicrobial activities. Compound 5e inhibited the growth of Methicillin resistant Staphylococcus aureus (MRSA) and Bacillus cereus and compound 5c inhibited Candida Pathogenic fungus at 50 μg/mL compared with the positive control (Nystatin) which inhibits Candida at 25 μg/mL.     

Antimicrobial and antiurease activities of newly synthesized morpholine derivatives containing an azole nucleus

2-[6-(Morpholin-4-yl)pyridin-3-ylamino]acetohydrazide (4) was obtained starting from 6-morpholin-4-ylpyridin-3-amine (2) via the formation of ester (3) and then converted to the corresponding Schiff bases (5, 6) with the reaction with aromatic aldehydes. The carbothioamide (9), obtained from the reaction of hydrazide with phenylisothiocyanate, was converted to the corresponding 1,2,4-triazole (11) and 1,3,4-thiadiazole (12) derivatives by the treatment with NaOH or H₂SO₄, respectively. The cyclocondenzation of 9 with 4-chlorophenacyl bromide or ethyl bromoacetate produced the corresponding 1,3-thiazole (10) or 1,3-thiazolidine derivatives (13), respectively. Antimicrobial and antiurease activities of newly synthesized compounds were investigated. Some of them were found to be active on M. smegmatis, and they displayed activity toward C. albicans and S. cerevisiae in high concentration. Compound 10 proved to be the most potent showing an enzyme inhibition activity with an IC₅₀ = 2.37 ± 0.19 μM.     

Synthesis, characterization, and antimicrobial activity of copper(II) complexes with N,N′-propanediyl-bis-benzenesulfonamide and N,N′-ethanediyl-bis-2-methylbenzenesulfonamide

Copper(II) complexes of new aryldisulfonamides (L ₁  = N,N′-bis[(2-methylphenyl)sulfonyl]ethylenediamine) and L ₂  = N,N′-propanediyl-bis-benzenesulfonamide with 1,10-phenanthroline have been synthesized and characterized by using elemental analyses, FT-IR, LCMS, conductivity, and magnetic susceptibility techniques. The structures of [Cu(phen)₂]L₁ (1) and [CuL₂(phen)₂] (2) compounds have been determined. Complex (1) has also been characterized by single crystal X-ray diffraction. The complex (1) crystallizes in the triclinic system, space group P1, with cell constants a = 12.9353(8) Å, b = 13.8543(9) Å, c = 14.4513(10) Å, α = 103.593(5)°, β = 113.713(5)°, γ = 106.104(5)°, and Z = 1. The antibacterial activities of synthesized compounds were studied against Gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis, and B. cereus and Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Yersinia enterocolitica by microdilution (as MICs in μg/mL) and disk diffusion (as diameter zone in mm) method. The biological activity screening showed that (1) has more activity than (2) against the tested bacteria.     

Synthesis and evaluation of new chalcones,derived pyrazoline and cyclohexenone derivatives as potent antimicrobial,antitubercular and antileishmanial agents

A series of chalcones (1–8) were prepared by Claisen–Schmidt condensation of 3-nitroacetophenone with various aldehydes. These chalcones on cyclization with hydrazine hydrate in the presence of glacial acetic acid, hydrazine hydrate in absolute ethanol and ethyl acetoacetate in the presence of barium hydroxide gave corresponding N-acetyl pyrazolines (9–16), N-unsubstituted pyrazolines (17–19) and cyclohexenone derivatives (20–22). All the synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity by using broth microdilution method, and many compounds showed promising activity against various tested bacteria and fungi. Among various tested compounds, 16 and 19 exhibited strongest activities against Streptococcus pyogenes and Pseudomonas aeruginosa; both have MIC value of 25 μg/mL, which is fourfold greater than the standard drug. Many compounds showed good activity against Candida albican. Analogs 11, 12, 15–17 and 19 displayed two- to fivefold greater activity against C. albican as compared to the standard drug. Results of antitubercular evaluation revealed that compounds 4 and 19 displayed strong antimycobacterial activity against H₃₇Rv having MIC of 25 and 62.5 μg/mL, respectively. All analogs were found to be inactive against Leishmania braziliensis except analogs 4 and 5 which exhibited strong leishmanicidal activity against Leishmania promastigotes with IC₅₀ values of 9.3 and 8.9 μg/mL, respectively.     

Flavonoids from Millettia nitida var. hirsutissima with their anticoagulative activities and inhibitory effects on NO production

Two new compounds, (2R)-7,3′-dihydroxy-6,4′-methoxyflavan (1) and (3R)-7,4′-dihydroxy-2′-methoxyisoflavan (2), along with 12 known flavonoids (3–14), were isolated from the vine stems of Millettia nitida var. hirsutissima. The structures of the isolated compounds were elucidated based on spectroscopic analyses and comparison of literature data. All of the isolates were evaluated for their effects on in-vitro anticoagulative assay and on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. As a result, all compounds showed weak antiplatelet aggregation activities and compounds 4, 5, 7, 8 and 9 demonstrated antithrombin activity with a good dose–effect relationship from 5 to 100 μg mL^?1 in rabbit plasma. Compounds 8, 9, 10 and 14 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 macrophages with IC₅₀ values of 4.79 ± 0.20, 8.23 ± 0.35, 5.23 ± 0.11 and 6.30 ± 0.30 μg mL^?1, respectively.     

In vitro cytotoxicity, antimicrobial, and metal-chelating activity of triterpene saponins from tea seed grown in Kangra valley, India

This study was undertaken to isolate and characterize saponins from seeds of Camellia sinensis. Four triterpene saponins S ₁ , S ₂ , S ₃ , and S ₄ were isolated by chromatography on silica (60–120 mesh), followed by purification on Sep-Pak C-18 columns. The chemical structures (S ₁ –S ₄ ) were elucidated on the basis of 1-D and 2-D NMR. All the saponins show broad-spectrum antifungal activity against Candida albicans, Issatchenkia orientalis, Aspergillus flavus, A. niger, A. ochraceous, A. parasiticus, A. sydowii, and Trichophyton rubrum. The most susceptible test fungus was T. rubrum inhibited at a minimum inhibitory concentration of 31.25 μg/ml by all the four saponins. Cytotoxicity of these saponins was evaluated by methyl thiazole tetrazolium and sulfo-rhodamine B assays. The saponins when tested against five human cancer cells lines, viz., OVCAR-5 (ovarian carcinoma cells), MCF-7 (human breast adenocarcinoma cells), PC-3 (human prostate cancer cells), Colo-205 (colorectal adenocarcinoma cells), and HL-60 (human promyelocytic leukemia cells) showed high cytotoxicity activity (99 %) by S ₁ and S ₂ on PC-3 cells at concentration of 100 μg/ml. Similarly, when these saponins were tested against human PBMCs by lymphocytes proliferation assay, none showed significant activity. S ₃ (IC₅₀ = 1.72 mg/ml) showed high metal-chelating activity at a concentration of 20 mg/ml.     

Antitumour activity of 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene] pyrimidine-2,4,6(1H,3H,5H)-triones against Dalton’s ascitic lymphoma in mice

A new series of novel benzimidazole derivatives containing barbitone moiety (5a–f) was synthesized by a Knoevenagel condensation of (2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ones (4a–f) and barbituric acid in the presence of catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, ¹H NMR and mass spectra analysis. Acute toxicity studies were performed initially to determine the safety of titled derivatives and the ED ₅₀ value was calculated 50 mg/kg. All the final derivatives were screened for antitumour activity against Dalton’s ascitic lymphoma in mice. All the new candidates at a dose of 50 mg/kg showed a good antitumour activity against DLA-bearing mice when compared to the standard 5-fluro uracil. Among the final derivatives (5e), 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-(3-nitrophenyl) prop-2-en-1-ylidene] pyrimidine-2,4,6(1H,3H,5H)-trione was found to be most potent antitumour in nature.     

Trypsin inhibitory potential and microbial transformation of rutin isolated from Citrus sinensis

This study was designed to determine the trypsin inhibitory potential of rutin (1) and its biotransformed metabolite, quercetin (2). Rutin (1) was purified from the methanolic extract of Citrus sinensis and biotransformed in the culture of Streptomyces griseus, which yielded quercetin (2) as the major product. Both 1 and 2 showed significant trypsin inhibitory potential with IC₅₀ = 0.016 ± 0.002 and 0.019 ± 0.003 mM, respectively. Kinetic studies were carried out using GraFit 7.0 software. Lineweaver–Burk and Dixon plots and their secondary replots indicated that these compounds are non-competitive inhibitors. The K _i values of 1 and 2 were found to be 17.5 ± 0.7 and 3.1 ± 0.5 μM, respectively.