Sorbent materials based on a hydrazone Schiff base compound, C(14)H(11)BrN(4)O(4), were prepared either by immobilizing the ligand into sol-gel (SG1) or bonding to silica (SG2). The sorbent materials were characterized by FT-IR, EDX, SEM, TEM, and TGA. The sorption characteristics of a matrix of eight transition metal ions (Ag(+), Cu(2+), Co(2+), Ni(2+), Fe(3+), Pb(2+), Zn(2+), and Mn(2+)) using batch method were studied. Several key parameters that affected the extraction efficiency such as pH, contact time, metal ions concentration, and gel size (for SGl) were investigated and optimized. Under the optimized conditions, the physically immobilized hydrazone sorbent (SG1) exhibits highest selectivity towards Ag(+) ions, while the chemically bonded hydrazone sorbent (SG2) exhibits high extraction for all metal ions tested. However, for practical applications such as the removal and preconcentration of Ag(+), the physically immobilized sorbent (SG1) is preferred.
Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.
Molecular hybridization yielded phenyl linked oxadiazole-benzohydrazones hybrids 6-35 and were evaluated for their antileishmanial potentials. Compound 10, a 3,4-dihydroxy analog with IC50 value of 0.95 ± 0.01 μM, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC50 = 7.02 ± 0.09 μM). The current series 6-35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC50 values ranging between 0.95 ± 0.01-78.6 ± 1.78 μM. Molecular docking analysis against pteridine reductase (PTR1) were also performed to probe the mode of action. Selectivity index showed that compounds with higher number of hydroxyl groups have low selectivity index. Theoretical stereochemical assignment was also done for certain derivatives by using density functional calculations.
Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.
The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis was assessed to evaluate the possible pathways induced by compound A and B. MTT assay results using A and B showed significant inhibition of MCF-7 cell viability, with IC50 values of 3. 27 ± 0.171 and 4.36 ± 0.219 μg/mL, respectively, after a 72 hour treatment period. Compound A and B did not demonstrate significant cytotoxic effects towards MDA-MB-231, WRL-68 and MCF-10A cells. Acute toxicity tests also revealed an absence of toxic effects on mice. Fluorescent microscopic studies confirmed distinct morphological changes (membrane blebbing and chromosome condensation) corresponding to typical apoptotic features in treated MCF-7 cells. Using Cellomics High Content Screening (HCS), we found that compound A and B could trigger the release of cytochrome c from mitochondria to the cytosol. The release of cytochrome c activated the expression of caspases-9 and then stimulated downstream executioner caspase-3/7. In addition, caspase-8 showed remarkable activity, followed by inhibition of NF-κB activation in A-and B-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways.
Free laccase and fungal biomass from white-rot fungi were compared in the thermokinetics study of the laccase-catalyzed decolorization of an azo dye, i.e., Trypan Blue. The decolorization in both systems followed a first-order kinetics. The apparent first-order rate constant, k1', value increases with temperature. Apparent activation energy of decolorization was similar for both systems at ∼ 22 kJ mol(-1), while energy for laccase inactivation was 18 kJ mol(-1). Although both systems were endothermic, fungal biomass showed higher enthalpy, entropy, and Gibbs free energy changes for the decolorization compared to free laccase. On the other hand, free laccase showed reaction spontaneity over a wider range of temperature (ΔT = 40 K) as opposed to fungal biomass (ΔT = 15 K). Comparison of entropy change (ΔS) values indicated metabolism of the dye by the biomass.
Some novel hydrazone derivatives 6a-o were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, ¹H-NMR, 13C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A₂ (sPLA₂), three protease enzymes and eleven bacterial strains were evaluated. The results revealed that all compounds showed preferential inhibition towards hGIIA isoform of sPLA₂ rather than DrG-IB with compounds 6l and 6e being the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease from Bacillus sp. with compound 6l being the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds; 6a, 6m, and 6o against P. aeruginosa; 6a, 6b, 6d, 6f, 6l, 6m, 6n, and 6o against Serratia; 6k against S. mutans; and compounds 6a, 6d, 6e, 6m, and 6n against E. feacalis. The docking simulations of hydrazones 6a-o with GIIA sPLA₂, proteinase K and hydrazones 6a-e with glutamine-fructose-6-phosphate transaminase were performed to obtain information regarding the mechanism of action.
A series of novel hydrazone compounds have been synthesized by the condensation of hydrazines and different substituted salicylaldehydes at a molar ratio of 1:1 in one step reaction and characterized by FT-IR, ESI-MS, 1H NMR, and single crystal x-ray diffraction. The crystal structure of the compound shows a trans configuration around the C = N bond and triclinic system with P -1/-p 1. Synthesized compounds were screened for cytotoxicity activities against A375 (melanoma), HT-29 (Colon), and A549 (lung) cancer cell lines. Among them, compound 2 exhibited the highest cytotoxic effect against the A375 cell line (IC50 = 0.30 µM) and HT-29 cell line (1.68 µM), compared to those of apatinib as a reference standard drug (0.28, 1.49 µM, respectively). The cytocompatibility assay on the L929 normal cell line and the hemolysis assay on human RBC were used to validate the non-toxic action. From DFT calculation, the various parameters such as HOMO-LUMO energies, Hirshfeld, and MEP have been studied. Furthermore, in silico molecular docking with three receptors was studied. Among four compounds, compound 2 has the lowest binding energy against cyclin dependent kinase (ΔGb = -9.3 kcal/mol). In addition to this, molecular dynamics (MD) simulation was also performed. Based on this study, these novel hydrazones can be considered a promising anticancer agent due to their potent cytotoxicity activities and computational analysis.Communicated by Ramaswamy H. Sarma.
2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.
Compounds 1-25 showed varying degree of antileishmanial activities with IC50 values ranging between 1.95 and 88.56 μM. Compounds 2, 10, and 11 (IC50=3.29±0.07 μM, 1.95±0.04 μM, and 2.49±0.03 μM, respectively) were found to be more active than standard pentamidine (IC50=5.09±0.04 μM). Compounds 7 (IC50=7.64±0.1 μM), 8 (IC50=13.17±0.46 μM), 18 (IC50=13.15±0.02 μM), and 24 (IC50=15.65±0.41 μM) exhibited good activities. Compounds 1, 3, 4, 5, 9, 12, 15, 18, and 19 were found to be moderately active. Compounds 13, 14, 16, 17, 20-25 showed weak activities with IC50 values ranging between 57 and 88 μM.
Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
A series of 4-methoxybenzoylhydrazones 1-30 was synthesized and the structures of the synthetic derivatives elucidated by spectroscopic methods. The compounds showed a varying degree of antiglycation activity, with IC50 values ranging between 216.52 and 748.71 µM, when compared to a rutin standard (IC50=294.46±1.50 µM). Compounds 1 (IC50=216.52±4.2 µM), 3 (IC50=289.58±2.64 µM), 6 (IC50=227.75±0.53 µM), 7 (IC50=242.53±6.1) and 11 (IC50=287.79±1.59) all showed more activity that the standard, and these compounds have the potential to serve as possible leads for drugs to inhibit protein glycation in diabetic patients. A preliminary SAR study was performed.
Five new anionic aqueous dioxidovanadium(V) complexes, [{VO2L1,2}A(H2O)n]α (1-5), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L1) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L2) incorporating different alkali metals (A = Na+, K+, Cs+) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1-5 were determined by time-dependent NMR and UV-vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2-4 confirmed the presence of vanadium(V) centers coordinated by two cis-oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1-5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC50 value of 5.42 ± 0.15 μM showed greater activity in comparison to cisplatin against the HT-29 cell line.
Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.
The crystal structure of the title compound, C(15)H(14)N(2)O(2). H(2)O, is in the keto tautomeric form and the configuration at the azomethine C=N double bond is E. The molecule is non-planar, with a dihedral angle of 27.3 (1) degrees between the aromatic rings. The crystal structure is stabilized by extensive hydrogen bonding involving the water molecule and hydrazone moiety.
Some novel 2,3-dioxo-5-(substituted)-arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra.
A new series of gallic hydrazones containing an indole moiety was synthesized through the reaction of gallic hydrazide and different indole carboxaldehydes. Their antioxidant activities were determined on DPPH radical scavenging and inhibition of lipid peroxidation. The in-vitro cytotoxic activities of the compounds were evaluated against HCT-116 (human colon cancer cell line) and MCF-7 (estrogen-dependent human breast cancer cell line) by the MTT method. An attempt to correlate the biological results with their structural characteristics has been done. A limited positive structure activity relationship was found between cytotoxic and antioxidant activities.
2,4-Dimethylbenzoylhydrazones 1-30 were synthesized by condensation reactions of 2,4-dimethylbenzoylhydrazide with various aromatic aldehydes and characterized. The assigned structures of compounds 10, 15 and 22 were further supported by single-crystal X-ray diffraction data. The synthesized compounds were evaluated for their in vitro DPPH radical scavenging activity. They exerted varying degree of scavenging activity toward DPPH radical with IC₅₀ values between 25.6-190 µM. Compounds 1, 4, 2, 3, 7, and 6 have IC₅₀ values of 25.6, 28.1, 29.3, 29.8, 30.0 and 30.1 µM respectively, showing better activity than an n-propyl gallate standard (IC₅₀ value = 30.30 µM). For super oxide anion scavenging activity compounds 1, 2 and 3 with IC₅₀ values of 98.3, 102.6, and 105.6, respectively, also showed better activity than the n-propyl gallate standard (IC₅₀ value = 106.34 µM).
In this research work, we report the synthesis and biological evaluation of two new series of 1-benzyl-4-(benzylidenehydrazono)-3,4-dihydro-1H-benzo[c] [1,2]thiazine 2,2-dioxides and 1-benzyl-4-((1-phenylethylidene)hydrazono)-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxides. The synthetic plan involves the mesylation of methyl anthranilate with subsequent N-benzylation of the product. The methyl 2-(N-benzylmethylsulfonamido)benzoate was subjected to cyclization reaction in the presence of sodium hydride to obtain 1-benzyl-1H-benzo[c][1,2]thiazin-4(3H)-one 2,2-dioxide which was treated with hydrazine hydrate to get corresponding hydrazone precursor. Finally, the titled compounds were obtained by reaction of hydrazone with various substituted aldehydes and ketones. The synthesized derivatives were subjected to carry out their inhibition activities against monoamine oxidases along with modelling investigations to evaluate their binding interactions and dynamic stability during the docking studies. The inhibition profile of potent compounds was found as competitive for both the isozymes. The compounds were more selective inhibitors of MAO-A as compared to MAO-B. Moreover, drug likeness profile of the derivatives was evaluated to have an additional insight into the physicochemical properties. The molecular dynamic simulations predicted the behaviour of amino acids with the active site residues.
Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Ureaplasma urealyticum, Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e, 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds.