Design, synthesis, and biological evaluation of piperazine derivatives involved in the 5-HT1AR/BDNF/PKA pathway.

In this study, four series of piperazine derivatives were designed, synthesised and subjected to biological test, and compound 6a with potential antidepressant activity was obtained. An affinity assay of compound 6a with 5-hydroxytryptamine (serotonin, 5-HT)1A receptor (5-HT1AR) was undertaken, and the effects on the 5-HT level in the brains of mice were also tested. The results showed that compound 6a had the best affinity with 5-HT1AR (Ki = 1.28 nM) and significantly increased the 5-HT level. The expression levels of 5-HT1AR, BDNF, and PKA in the hippocampus were analysed by western blot and immunohistochemistry analyses. The results showed that the expression of 5-HT1AR, BDNF, and PKA in the model group was reduced compared to that of the control group, and compound 6a could reverse this phenomenon. Molecular docking was performed to investigate the interactions of the studied compound 6a with 5-HT1AR on the molecular level.

Evaluation of anti-glioma effects of benzothiazoles as efficient apoptosis inducers and DNA cleaving agents.

Glioma is the fast-growing, aggressive, and prevalent brain cancer with a great level of morbidity and mortality. Current therapy is usually found insufficient for glioma treatment. In the course of our research attempting to identify effective anti-glioma agents, three benzothiazole derivatives (1-3) were examined on U251 glioma cells. Among these derivatives, compound 3 was found to have the strongest cytotoxic effect on glioma cells with an IC50 value of 9.84 ± 0.64 µM in reference to cisplatin (IC50 = 8.41 ± 1.27 µM). Further mechanism of anti-glioma effects of compound 3 was characterized by the determination of its apoptotic effects in glioma cells and DNA cleaving capacity. Compound 3 caused a significant apoptotic death of U251 cell line. Besides, this compound cleaved DNA with FeSO4, H2O2 and ascorbic acid system. Molecular docking results also showed that compound 3 possessed a significant binding potential to DNA via important π-π stacking interaction with DG-16. Some pharmacokinetic determinants of compound 3 complied with standard limits making it as an efficient bioavailable anti-glioma drug candidate for upcoming exploration.

Oxadiazole Schiff Base as Fe3+ Ion Chemosensor: "Turn-off" Fluorescent, Biological and Computational Studies.

Compound, (E)-5-(4-((thiophen-2-ylmethylene)amino)phenyl)-1,3,4-oxadiazole-2-thiol (3) was synthesized via condensation reaction of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol with thiophene-2-carbaldehyde in ethanol. For the synthesis and structural confirmation the FT-IR, 1H, 13C-NMR, UV-visible spectroscopy, and mass spectrometry were carried out. The long-term stability of the probe (3) was validated by the experimental as well as theoretical studies. The sensing behaviour of the compound 3 was monitored with various metal ions (Ca2+, Cr3+, Fe3+, Co2+, Mg2+, Na+, Ni2+, K+) using UV- Vis. and fluorescence spectroscopy techniques by various methods (effect of pH and density functional theory) which showing the most potent sensing behaviour with iron. Job's plot analysis confirmed the binding stoichiometry ratio 1:1 of Fe3+ ion and compound 3. The limit of detection (LOD), the limit of quantification (LOQ), and association constant (Ka) were calculated as 0.113 µM, 0.375 µM, and 5.226 × 105 respectively. The sensing behavior was further confirmed through spectroscopic techniques (FT-IR and 1H-NMR) and DFT calculations. The intercalative mode of binding of oxadiazole derivative 3 with Ct-DNA was supported through UV-Vis spectroscopy, fluorescence spectroscopy, viscosity, cyclic voltammetry, and circular dichroism measurements. The binding constant, Gibb's free energy, and stern-volmer constant were find out as 1.24 × 105, -29.057 kJ/mol, and 1.82 × 105 respectively. The cleavage activity of pBR322 plasmid DNA was also observed at 3 × 10-5 M concentration of compound 3. The computational binding score through molecular docking study was obtained as -7.4 kcal/mol. Additionally, the antifungal activity for compound 3 was also screened using broth dilution and disc diffusion method against C. albicans strain. The synthesized compound 3 showed good potential scavenging antioxidant activity against DPPH and H2O2 free radicals.

Synthesis, biological evaluation, and molecular docking studies of aldotetronic acid-based LpxC inhibitors.

In order to develop novel inhibitors of the bacterial deacetylase LpxC bearing a substituent to target the UDP binding site of the enzyme, a series of aldotetronic acid-based hydroxamic acids was accessed in chiral pool syntheses starting from 4,6-O-benzylidene-d-glucose and l-arabinitol. The synthesized hydroxamic acids were tested for LpxC inhibitory activity in vitro, revealing benzyl ether 17a ((2S,3S)-4-(benzyloxy)-N,3-dihydroxy-2-[(4-{[4-(morpholinomethyl)phenyl]ethynyl}benzyl)oxy]butanamide) as the most potent LpxC inhibitor. This compound was additionally tested for antibacterial activity against a panel of clinically relevant Gram-negative bacteria, bacterial uptake, and susceptibility to efflux pumps. Molecular docking studies were performed to rationalize the observed structure-activity relationships.

New antiproliferative 3-substituted oxindoles inhibiting EGFR/VEGFR-2 and tubulin polymerization.

New 3-substituted oxindole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of compounds 6a-j was evaluated against 60 NCI cell lines. Among these tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity, specifically against leukemia and breast cancer cell lines. Compound 6f was the most promising antiproliferative agent against MCF-7 (human breast cancer) with an IC50 value of 14.77 µM compared to 5-fluorouracil (5FU) (IC50 = 2.02 µM). Notably, compound 6f hampered receptor tyrosine EGFR fundamentally with an IC50 value of 1.38 µM, compared to the reference sunitinib with an IC50 value of 0.08 µM. Moreover, compound 6f afforded anti-tubulin polymerization activity with an IC50 value of 7.99 µM as an outstanding observable activity compared with the reference combretastatin A4 with an IC50 value of 2.64 µM. In silico molecular-docking results of compound 6f in the ATP-binding site of EGFR agreed with the in vitro results. Besides, the investigation of the physicochemical properties of compound 6f via the egg-boiled method clarified good lipophilicity, GIT absorption, and blood-brain barrier penetration properties.

Design and synthesis of novel quinazolinyl-bisspirooxindoles as potent anti-tubercular agents: an ultrasound-promoted methodology.

The essential need for the potent anti-tubercular (anti-TB) agents with high selectivity and safety profile prompted us to synthesize a new series of quinazolinyl-bisspirooxindoles. The title compounds were synthesized by one-pot multicomponent [3 + 2] cycloaddition reaction under ultrasonication. Further, in vitro anti-TB activity was evaluated against Mycobacterium tuberculosis H37Rv. Among the screened compounds, two compounds (4q and 4x) showed potent activity with MIC value 1.56 µg/mL and four compounds exhibited significant activity (MIC = 3.125 µg/mL), and also cytotoxicity studies against RAW 264.7 cell lines reveal that most active compounds were less toxic to humans. In addition, in order to demonstrate the inhibitory properties, molecular docking studies were carried out and the results showed that the target compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may consider to be as potent inhibitors toward selective targets.

Synthesis, antidiabetic activity and molecular docking studies of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles.

A series of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles synthesized in a straightforward route consisting of benzylidenethiazolidine-2,4-dione and 1,2,3-triazole pharmacophores. The new scaffolds tested for in vitro antidiabetic activity by inhibition of aldose reductase enzyme and its inhibition measured in half of Inhibition Concentration (IC50). The activity results correlated with standard reference Sorbinil (IC50: 3.45 ± 0.25 µM). Among all the titled compounds 8f (1.42 ± 0.21 µM), 8d (1.85 ± 0.39 µM), 13a (1.94 ± 0.27 µM) and 8b (1.98 ± 0.58 µM) shown potent activity. In addition, molecular docking results against the crystal structure of aldose reductase (PDB ID: 1PWM) revealed that the binding affinities shown by all synthesized compounds are higher than the reference compound Sorbinil. The docking scores, H-bond interactions, and hydrophobic interactions well defined inhibition strength of all compounds.

Synthesis, Anticancer Evaluation and in Silico Studies of 1,4-Dihydropyridines.

An efficient 1,4-dihydropyridine synthesis under mild conditions has been developed. Numerous substrates were tested, with yields of 1,4-dihydropridines ranging from good to excellent and a wide range of functional group tolerance. A549, HT-29, and HepG2 cancer cells were used to investigate the anticancer efficacy of each of the produced compounds. Additionally, in-silico docking studies were conducted to understand the structure-based features of the anticancer mechanism with the cancer medication target of Adenosine A2A receptor as well as the molecular level interactions of the compounds.

Design, Synthesis, Molecular Docking, and Molecular Dynamics Simulation Studies of Novel 3-Hydroxypyridine-4-one Derivatives as Potential Acetylcholinesterase Inhibitors.

Researchers have focused on inhibiting acetylcholinesterase for Alzheimer's disease treatment. In this study, some novel AChE inhibitors were synthesized using hydroxypyridin-4-one plus benzylpiperidine scaffolds which were evaluated using Ellman's method. Accordingly, ((1-(4-methoxyphenethyl)piperidin-4-yl)amino)methyl)-5-hydroxy-1-methylpyridin-4(1H)-one (VIId ) showed weaker but promising AChE inhibition compared to donepezil (IC50 =143.090 nM). The average RMSD values of VIId was found to be 2.25 indicated less structural changes in the active site residues. The phenyl group of the phenyl-ethyl-N-piperidine moiety of VIId formed hydrophobic interactions with Trp285 and Tyr340. There was a π-cation interaction between nitrogen atom of piperidine ring and Phe294. Another π-cation interaction was found between type 2 amine of linker and Trp85. Piperidine ring interacted with Tyr336, Tyr123, and Phe337 through hydrophobic interactions. Indeed, the VIId was predicted to be absorbed across the gastrointestinal tract, though it may be pumped out by P-gp. Indeed, VIId can permeate through the blood brain barrier. MD simulation studies revealed that benzyloxy moiety plays a role similar to benzylpiperidine moiety of donepezil in binding to the active site residues. Also, carbonyl group functioned similar to indanone ketone group. Overall; further research on VIId may lead to introduction of a novel class of AChE inhibitors.

Discovery of novel thioquinazoline-N-aryl-acetamide/N-arylacetohydrazide hybrids as anti-SARS-CoV-2 agents: Synthesis, in vitro biological evaluation, and molecular docking studies.

In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on Mpro binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.

Natural-Product-Inspired Microwave-Assisted Synthesis of Novel Spirooxindoles as Antileishmanial Agents: Synthesis, Stereochemical Assignment, Bioevaluation, SAR, and Molecular Docking Studies.

Leishmaniasis is a neglected tropical disease, and there is an emerging need for the development of effective drugs to treat it. To identify novel compounds with antileishmanial properties, a novel series of functionalized spiro[indoline-3,2'-pyrrolidin]-2-one/spiro[indoline-3,3'-pyrrolizin]-2-one 23a-f, 24a-f, and 25a-g were prepared from natural-product-inspired pharmaceutically privileged bioactive sub-structures, i.e., isatins 20a-h, various substituted chalcones 21a-f, and 22a-c amino acids, via 1,3-dipolar cycloaddition reactions in MeOH at 80 °C using a microwave-assisted approach. Compared to traditional methods, microwave-assisted synthesis produces higher yields and better quality, and it takes less time. We report here the in vitro antileishmanial activity against Leishmania donovani and SAR studies. The analogues 24a, 24e, 24f, and 25d were found to be the most active compounds of the series and showed IC50 values of 2.43 µM, 0.96 µM, 1.62 µM, and 3.55 µM, respectively, compared to the standard reference drug Amphotericin B (IC50 = 0.060 µM). All compounds were assessed for Leishmania DNA topoisomerase type IB inhibition activity using the standard drug Camptothecin, and 24a, 24e, 24f, and 25d showed potential results. In order to further validate the experimental results and gain a deeper understanding of the binding manner of such compounds, molecular docking studies were also performed. The stereochemistry of the novel functionalized spirooxindole derivatives was confirmed by single-crystal X-ray crystallography studies.

Drug Repurposing to Inhibit Histamine N-Methyl Transferase.

Lower activity of the histaminergic system is associated with neurological disorders, including Alzheimer's disease (AD). Thus, the enhancement of histaminergic neurotransmission by inhibition of histamine N-methyl transferase (HNMT), which degrades histamine, appears as an important approach. For this purpose, rigid and flexible molecular docking studies of 185 FDA-approved drugs with the HNMT enzyme were carried out to select two compounds to perform molecular dynamics (MD) simulations to evaluate the binding free energies and stability of the enzyme-drug complexes. Finally, an HNMT inhibition assay was performed to corroborate their effect towards HNMT. Molecular docking studies with HNMT allowed the selection of dihydroergotamine and vilazodone since these molecules showed the lowest Gibbs free energy values. Analysis of the binding mode of vilazodone showed interactions with the binding pocket of HNMT with Glu28, Gln143, and Asn283. In contrast, dihydroergotamine binds to the HNMT active site in a different location, apparently because it is overall the more rigid ligand compared to flexible vilazodone. HNMT inhibitory activity for dihydroergotamine and vilazodone was corroborated (IC50 = 72.89 µM and 45.01 µM, respectively) by in vitro assays. Drug repurposing of HNMT was achieved by employing computational studies.

Synthesis, biological evaluation and molecular docking studies of novel diosgenin derivatives as anti-inflammatory agents.

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.

Identification of thienopyrimidine glycinates as selective inhibitors for h-NTPDases.

The h-NTPDases is an essential family of ectonucleotidases that consists of eight isozymes with various physiological functions. The undesired activity of the h-NTPDases leads to pathological conditions such as cancer, diabetes, inflammation, and thrombosis. In the present study, a series of thienopyrimidines was synthesized employing a sequential SNAr and Suzuki coupling to synthesize diverse aryl substituted thienopyrimidine glycinate derivatives. The synthesized compounds constituted electron donating, electron-deficient, heteroaryl, and fluorinated substituents. The thienopyrimidines were screened against h-NTPDases to determine the effect on the activity of the h-NTPDases-1, -2, -3, and -8. The compound 3j selectively blocked the isozyme h-NTPDases1, while the compounds 3e, 3m, and 4a were selective inhibitors of h-NTPDases2. The activity of the isozyme h-NTPDases3 was selectively reduced by inhibitor 3k whereas, the compound 3d was found as the most active inhibitor against isozyme h-NTPDase8. The molecular docking study interpreted the interactions of the potent inhibitors of the respective isozymes with important amino acid residues i.e., Asp54, Ser57, His59, Ser58, His59, Asp213, and Phe360 of h-NTPDases1 protein; residues Arg 392, Ala393, Ala347, Tye350 and Arg245 of h-NTPDases2; amino acids Arg67, Ser65, Ala323, Gly222, and Tyr375 of h-NTPDases3 whereas in case of h-NTPDases8, the residues Val436, Gln74, Gly179, and Val71 were involved in interaction with the inhibitors docked into the active sites of these isozymes.

Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity.

A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best anticancer potential in all tested cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon cancer cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and downregulation of AKT pathway. Similarly, 5b treatment induced caspase-3 cleavage which is a hallmark of apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).

Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates.

This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10-30 µM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa), & 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.

Ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates: Silica supported bismuth(III)triflate catalyzed synthesis and antioxidant activity.

Novel ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates were synthesized from one-pot, three-component Biginelli reaction of aryl aldehydes, ethyl acetoacetate and urea/ thiourea by catalytic action of silica supported Bismuth(III) triflate, a Lewis acid. All the synthesized compounds were structurally characterized by spectral (IR, 1H NMR & 13C NMR spectroscopic and Mass spectrometric) and elemental (C, H & N) analyses. The present protocol has deserved novel as, formed the products in high yields with short reaction times, involved eco-friendly methodology and reusable heterogeneous Lewis acid catalyst. The title compounds were screened for in vitro DPPH free radical scavenging antioxidant activity and identified 4i, 4j, 4h & 4f as potential antioxidants. The obtained in vitro results were correlated with molecular docking, ADMET, QSAR, Bioactivity & toxicity risk studies and molecular finger print properties and found that in silico binding affinities were identified in good correlation with in vitro antioxidant activity and studied the structure activity relationship. The molecular docking study has disclosed strong hydrogen bonding interactions of title compounds with aspartic acid (ASP197) aminoacid residue of 2HCK, a complex enzyme of haematopoietic cell kinase and quercetin. Results of toxicology study evaluated for potential risks of compounds have revealed title compounds as safer drugs. In ultimate the study has established ligand's antioxidant potentiality as they effectively binds with ASP197 amino acid of Chain A hence confirms the inhibition of growth of reactive oxygen species in vivo. In addition, the title compounds have been identified as potential blood-brain barrier penetrable entities and efficient central nervous system (CNS) active neuro-protective antioxidant agents.

Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies.

Thiazole derivatives are known inhibitors of alkaline phosphatase, but various side effects have reduced their curative efficacy. Conversely, compounds bearing azomethine linkage display a broad spectrum of biological applications. Therefore, combining the two scaffolds in a single structural unit should result in joint beneficial effects of both. A new series of azomethine-clubbed thiazoles (3a-i) was synthesized and appraised for their inhibitory potential against human tissue non-specific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). Compounds 3c and 3f were found to be most potent compounds toward h-TNAP with IC50 values of 0.15 ± 0.01 and 0.50 ± 0.01 µM, respectively, whereas 3a and 3f exhibited maximum potency for h-IAP with IC50 value of 2.59 ± 0.04 and 2.56 ± 0.02 µM, respectively. Molecular docking studies were also performed to find the type of binding interaction between potential inhibitor and active sites of enzymes. The enzymes inhibition kinetics studies were carried out to define the mechanism of enzyme inhibition. The current study leads to discovery of some potent inhibitors of alkaline phosphatase that is promising toward identification of compounds with druggable properties.

2-Amino-5-substituted-1,3,4-oxadiazole as chemosensor for Ni(II) ion detection: antifungal, antioxidant, DNA binding, and molecular docking studies.

An oxadiazole derivative 2 was prepared by condensation reaction through cyclization of semicarbazone in the presence of bromine; the structural confirmation was supported by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform-infrared spectroscopy, and liquid chromatography-mass spectrometry. Its sensing ability towards Ni2+ ion was examined showing a binding constant of 1.04 × 105 compared with other suitable metal cations (Ca2+ , Co2+ , Cr3+ , Ag+ , Pb2+ , Fe3+ , Mg2+ , and K+ ) using ultraviolet-visible (UV-vis) and fluorescence spectroscopic studies. The minimum concentration of Ni2+ ions and limit of detection was found to be 9.4 µM. A job's plot gave the binding stoichiometry ratio of oxadiazole derivative 2 vs Ni2+ ions as 2:1. Furthermore, the intercalative binding mode of oxadiazole derivative 2 with calf thymus DNA was supported by ultraviolet-visible (UV-vis) and fluorescent light, viscosity, cyclic voltammetry, time-resolved fluorescence, and circular dichroism measurements. The molecular docking result gave the binding score for oxadiazole derivative 2 as -6.5 kcal/mol, which further confirmed the intercalative interaction. In addition, the antifungal activity of oxadiazole derivative 2 was also screened against several fungal strains (C. albicans, C. glabrata, and C. tropicalis) by broth dilution and disc diffusion methods. In antioxidant studies, the oxadiazole derivative 2 showed potential scavenging activity against 2,2-diphenyl-1-picrylhydrazyl and H2 O2 free radicals.

Enzyme Inhibition Properties and Molecular Docking Studies of 4-Sulfonate Containing Aryl α-Hydroxyphosphonates Based Hybrid Molecules.

In this study, a series of new hybrid molecules containing two important functional groups on the same skeleton were designed. 4-Hydroxybenzaldehyde and its two different derivatives were converted into their respective sulphonates by interacting with tosylchloride and methanesulfonyl chloride. Then, the desired molecules were synthesized by adding diethoxyphosphonate to the aldehyde group. Also, novel synthesis of hybrid compounds (4a-c and 5a-c) were tested toward some metabolic enzymes like carbonic anhydrase I and II isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme. The synthesis of hybrid compounds (4a-c and 5a-c) showed Ki values of in range of 25.084±4.73-69.853±15.19 nM against hCA I, 32.325±1.67-82.761±22.73 nM against hCA II and 1.699±0.25 and 3.500±0.91 nM against AChE. For these compounds, compound 4c showed maximum inhibition effect against hCA I and hCA II isoenzymes and compound 5b showed maximum inhibition effect against AChE enzyme. By performing docking studies of the most active compounds for their binding modes and interactions were determined.