Tanzeela Abdul Fattah

Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors

In this article, synthesis of a novel 1‐(2‐(4‐isobutylphenyl)propanoyl)‐3‐arylthioureas (4a–j) as jack bean urease inhibitors has been described. Freshly prepared 2‐(4‐isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC50 values 0.0086 nm, 0.0081 nm, and 0.0094 nm, respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm. The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm, respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors.

Enzyme inhibitory activities an insight into the structure–Activity relationship of biscoumarin derivatives

Biscoumarin derivatives, a dimeric form of coumarin, are well known derivatives of coumarin, occurred in the bioactive metabolites of marine and terrestrial organisms. On account of pharmacological and biological applications, biscoumarins have long been the subject of innumerable enzyme inhibition studies. In this review the pros and cons of enzyme inhibition studies of biscoumarins as urease inhibitors, aromatase inhibitors, NPPs, α-glucosidase inhibitors, α-amylase inhibitors, HIV-1 integrase inhibition, steroid sulfatase inhibitors and c-Met inhibitors are discussed in a systematic way. Moreover, the review discusses the structure activity relationship of biscoumarin scaffold with enzyme inhibitory potency which would unleash new avenues for further development. The purpose of the current review is to disclose the value of biscoumarins as potent and efficient enzyme inhibitor. This review provides a guideline to elaborate the diversity of biscoumarin inhibitors by exploring the effects of electronic groups linked with biscoumarin nucleus.

DABCO–PEG ionic liquid-based synthesis of acridine analogous and its inhibitory activity on alkaline phosphatase

ABSTRACT In world, many people struggle with viral, parasitic, bacterial, cancer, and other diseases. Therefore, numerous chemists seek to develop less toxic, more selective, and effective medicines. Most therapeutic medicines are based on inhibition of specific enzymes. Acridines are interesting heterocyclic structures that are much sought after targets attributed to their wide biological activities and feature to display potent enzymes inhibitory effects. Their approach of action is owing to DNA interaction and subsequent effects on the biological functions linked to DNA and associated enzymes. In this regards, we synthesized acridine analogous through 1,4-diazabicyclo[2.2.2]octane (DABCO)–polyethylene glycol-400 (PEG-400) mediated ionic liquid approach. DABCO–PEG-400-mediated IL was prepared through the DABCO alkylation using 1-bromopentane followed by mixing with PEG-400. The synthesized analogous were investigated as inhibitors of alkaline phosphatase, which is a nonspecific phosphomonoester hydrolase that catalyzes the hydrolysis of broad spectrum of organic monophosphates. Analogue viz. 3,3,6,6-tetramethyl-9-(4-nitrophenyl)-2,3,4,5,6,7,9,10-octahydroacridine-1,8-dione was found to be potent alkaline phosphatase inhibitor. GRAPHICAL ABSTRACT

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

The present article illustrated the synthesis and characterization of a novel series of (E)-4-(substituted-benzylideneamino)-2H-chromen-2-one derivatives 4A-4J: in good to excellent yields. The target compounds were synthesized by refluxing 4-aminocoumarin with aromatic aldehydes in ethanol. The structural confirmation was achieved by spectroscopic techniques such as (1H, 13C-NMR and FT-IR) and elemental analysis. The synthesized compounds were evaluated for carbonic anhydrase II (CA-II) inhibition and free radical scavenging activity. All the compounds showed CA-II inhibition in the micro molar range. The compound 4C: exhibited higher potential in the series with IC50=0.0928±0.00545 µM (standard Acetazolamide IC50=0.997±0.0586 µM). Pharmacological investigations showed that the synthesized compounds 4A-4J: obey Lipinsks rule. Compound 4C: elicited drug likeness and showed drug score value of 0.05. Molecular docking analysis showed that compound 4C: interacts with Asn66 and Gln91 amino acid residues. Graphical Abstract.

Applications of Keck allylation in the synthesis of natural products

This review highlights the applications of the Keck allylation reaction in the synthesis of medicinally important natural products. Keck allylation is a versatile chemical reaction used for the conversion of a variety of aldehydes into homoallylic alcohols and has many applications in the synthesis of biologically active natural products. Efforts have been made to comprehensively provide an overview of the role of the Keck allylation reaction in the synthesis of natural products including the synthesis of macrolides, phorboxazole B, mandelalide A, rhizopodin, palmerolide A, belactosin A and hormaomycin, bryostatin I, the anti-tumor drug epothilones B, and the anti-obesity drug orlistat. This review will be beneficial for the biological and synthetic communities.

3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV

We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a-k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5-44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35-37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.

A review on the Scope of Fluorinated Selective and Reactive TFDO-Mediated Oxidation in Organic Synthesis

Dioxiranes are three-membered strained ring peroxides that are typical archetype examples of electrophilic entities. A dioxirane-based oxidant named 3-methyl(trifluoromethyl)dioxirane (TFDO) is a f ...

General properties and comparison of the corrosion inhibition efficiencies of the triazole derivatives for mild steel

Abstract Mild steel (MS) corrosion is a worldwide issue that greatly affects the industrial and natural environment. To extend the lifespan of appliances, the control of MS corrosion is necessary. To shield MS from corrosion, specifically from acidic conditions, one of the practical and finest approaches is the application of inhibitors. Triazole derivatives are eco-friendly corrosion inhibitors (CIs) having inconsequential toxicities, excellent inhibition efficiencies (IEs) against corrosion of MS, and extremely high cost-effectiveness. This critical review discusses the general effect of temperature, concentration, time after the application of CI, and type of acid on the IE of triazole derivatives. Further, the review provides an adequate amount of information about the features of excellent CIs; a summary of the reported properties of triazole-based inhibitors, CIs in industries, and current requirements of industries; and recommendations and implications for researchers to improve IE. Additionally, the review also illustrates the mechanisms of action and the IEs, which are evaluated from potentiodynamic polarization parameters, in various acidic media and concentrations of triazole inhibitors. By IE correlation with numerous concentrations and acidic conditions, this review is advantageous and helpful for synthetic chemists to expand the diversity and complexity of a class of triazole derivatives by synthesizing new triazole derivatives.

Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, pharmacokinetic properties, lead optimization, Lineweaver-Burk plot evaluation and binding analysis

To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series (4a-4j) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis. The synthesized derivatives 4a-4j were subjected to calf intestinal alkaline phosphatase (CIAP) activity. The derivative 4a-4j showed better inhibition potential compared to standard monopotassium phosphate (MKP). The compound 4c exhibited higher potential in the series with IC50 0.251 ± 0.012 µM (standard KH2PO4 4.317 ± 0.201 µM). Lineweaver-Burk plots revealed that most potent derivative 4c inhibition CIAP via mixed type pathway. Pharmacological investigations showed that synthesized compounds 4a-4j obey Lipinsks rule. ADMET parameters evaluation predicted that these molecule show significant lead like properties with minimum possible toxicity and can serve as templates in drug designing. The synthetic compounds show none mutagenic and irritant behavior. Molecular docking analysis showed that compound 4c interacts with Asp273, His317 and Arg166 amino acid residues.

Synthesis, computational studies and enzyme inhibitory kinetics of substituted methyl[2-(4-dimethylamino-benzylidene)-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates as mushroom tyrosinase inhibitors

The present article describes the synthesis and enzyme inhibitory kinetics of methyl[2-(arylmethylene-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates 5a-j as mushroom tyrosinase inhibitors. The title compounds were synthesized via cyclocondensation of thiosemicarbazones 3a-j with dimethyl but-2-ynedioate (DMAD) 4 in good yields under solvent-free conditions. The synthesized compounds were evaluated for their potential to inhibit the activity of mushroom tyrosinase. It was unveiled that compounds 5i showed excellent enzyme inhibitory activity with IC50 3.17µM while IC50 of standard kojic acid is 15.91µM. The presence of heterocyclic pyridine ring in compound 5i play important role in enzyme inhibitory activity as rest of the functional groups are common in all synthesized compounds. The enzyme inhibitory kinetics of the most potent derivative 5i determined by Lineweaver-Burk plots and Dixon plots showed that it is non-competitive inhibitor with Ki value 1.5µM. It was further investigated that the wet lab results are in good agreement with the computational results. The molecular docking of the synthesized compounds was performed against tyrosinase protein (PDBID 2Y9X) to delineate ligand-protein interactions at molecular level. The docking results showed that the major interacting residues are His244, His85, His263, Val 283, His 296, Asn260, Val248, His260, His261 and Phe264 which are located in active binding site of the protein. The molecular modeling demonstrates that the oxygen atom of the compound 5i coordinated with the key residues in the active site of mushroom tyrosinase contribute significantly against inhibitory ability and diminishing the human melanin synthesis. These results evident that compound 5i is a lead structure in developing most potent mushroom tyrosinase inhibitors.