Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Using Quantum Mechanical Fragment Molecular Orbital-Based Virtual Screening Methods.

Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow.

Synthesis, Kinetics, Binding Conformations and Structure-activity Relationship of Potent Tyrosinase Inhibitors: Aralkylated 2-aminothiazole-ethyltriazole Hybrids.

Considering the diversified pharmacological importance of thiazole and triazole heterocyclic moieties, a unique series of -aralkylated bi-heterocyclic hybrids, , was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by H-NMR, C-NMR, IR, and EI-MS spectral studies. The structure-activity relationship of these compounds was envisaged by analyzing their inhibitory effects against tyrosinase, whereby all these molecules exhibited potent inhibitory potentials relative to the standard used.

Novel 1,3,4-oxadiazole compounds inhibit the tyrosinase and melanin level: Synthesis, in-vitro, and in-silico studies.

In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, H NMR and C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed.

Synthesis of Bi-heterocyclic Sulfonamides as Tyrosinase Inhibitors: Lineweaver-Burk Plot Evaluation and Computational Ascriptions.

The designed bi-heterocyclic sulfonamides were synthesized through a two-step protocol and their structures were ascertained by spectral techniques including IR, 1H NMR and 13C NMR along with CHN analysis. The in vitro inhibitory effects of these sulfonamides were evaluated against tyrosinase and kinetics mechanism was analyzed by Lineweaver-Burk plots. The binding modes of these molecules were ascribed through molecular docking studies.

Identification of novel C-2 symmetric Bis-Azo-Azamethine molecules as competitive inhibitors of mushroom tyrosinase and free radical scavengers: synthesis, kinetics, and molecular docking studies.

Tyrosinase is a multi-copper enzyme found in plants, animals and microorganisms, plays a critical role in the melanogenesis and browning process critical to cosmetics and food industries. Many natural, semi-synthetic and synthetic inhibitors have been discovered. To this end, a small library of symmetrical Bis-Azo-Azamethine hybrids was synthesized and characterized through spectroscopic and analytical data and explored for mushroom tyrosinase and free radical scavenging activity.

Novel Bi-heterocycles as Potent Inhibitors of Urease and Less Cytotoxic Agents: 3-({5-((2-Amino-1,3-thiazol-4-yl)methyl)-1,3,4-oxadiazol-2-yl}sulfanyl)--(un/substituted-phenyl)propanamides.

The synthesis of a novel series of bi-heterocyclic propanamides, , was accomplished by -substitution of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (). The synthesis was initiated from ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate () which was converted to corresponding hydrazide, , by hydrazine hydrate in methanol. The refluxing of hydrazide, , with carbon disulfide in basic medium, resulted in 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol ().

Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors.

Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains ( to ) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC = 16.

Synthesis of novel xanthene based analogues: Their optical properties, jack bean urease inhibition and molecular modelling studies.

In this work, a series of the rhodamine 6G based derivatives 5a-5g, were synthesized. The structural framework of the synthesized compounds was established by using H NMR, C NMR, FT-IR, and LC-MS analytical methods. The spectroscopic properties of the target compounds were determined by using absorption and fluorescence study in four different solvents.

Synthesis and characterization of new 4H-chromene-3-carboxylates ensuring potent elastase inhibition activity along with their molecular docking and chemoinformatics properties.

A new series of 4H-chromene-3-carboxylate derivatives were synthesized using multicomponent reaction of salicylaldehyde, ethyl acetoacetate and dimedone in ethanol with KPO as a catalyst at 80 °C. The structures of all newly synthesized compounds were confirmed by spectral techniques viz. IR, H NMR, C NMR, and LCMS analysis.

Novel 1,2,4-triazole analogues as mushroom tyrosinase inhibitors: synthesis, kinetic mechanism, cytotoxicity and computational studies.

We have created a novel series of mushroom tyrosinase inhibitors with 1,2,4-triazole as fundamental skeleton. The target compound 1,2,4-triazol-3-ylthio)-N-phenyl acetamide derivatives 9(a-l) were synthesized by the reaction of 4- and 5-substituted 1,2,4-triazole-3-thiol derivatives 6(a-c) with 2-chloro-N-sub/un-substituted phenyl acetamide derivatives 8(a-d) under basic condition. By using the analytical techniques for instance, FTIR, LC-MS, H NMR and C NMR, the structural verification was evaluated.

Design and Synthesis of New Porphyrin Analogues as Potent Photosensitizers for Photodynamic Therapy: Spectroscopic Approach.

New porphyrin analogues have been designed and synthesized using pyrrole, various aldehydes and propionic acid. The formation of desired compounds was analyzed by utilizing the spectral analysis such as IR, NMR and Mass spectroscopy. The studies on absorption and fluorescence emission of synthesized porphyrins were used to evaluate photophysical characteristics such as molar excitation coefficient and Stokes shift.

Synthesis, molecular docking, dynamic simulations, kinetic mechanism, cytotoxicity evaluation of N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl} butanamides as tyrosinase and melanin inhibitors: In vitro, in vivo and in silico approaches.

In the current research work, different N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides have been synthesized according to the protocol described in scheme 1. The synthesis was initiated by reacting various substituted anilines (1a-e) with 4-chlorobutanoyl chloride (2) in aqueous basic medium to give various electrophiles, 4-chloro-N-(substituted-phenyl)butanamides (3a-e). These electrophiles were then coupled with 1-[(E)-3-phenyl-2-propenyl]piperazine (4) in polar aprotic medium to attain the targeted N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides (5a-e).

Synthesis and exploration of a novel chlorobenzylated 2-aminothiazole-phenyltriazole hybrid as migratory inhibitor of B16F10 in melanoma cells.

In the study presented here, a novel chlorobenzylated bi-heterocyclic hybrid molecule () was synthesized and its structural confirmation was carried out by IR, H-NMR, C-NMR and CHN analysis data. This compound was subjected to biological study with B16F10 mouse melanoma cells. The anti-proliferative results showed that showed no significant toxicity at concentrations ranging of 0-44 μM.

Designing of promising medicinal scaffolds for Alzheimer's disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches.

In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer's disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells.

Ultrasound mediated efficient synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamides as potent tyrosinase inhibitors: Mechanistic approach through chemoinformatics and molecular docking studies.

We have carried out the synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamide derivatives by the reaction between isatoic anhydride, 2-furoic hydrazide and substituted salicylaldehydes in ethanol: water (5:5 v/v) solvent system using p-TSA as a catalyst under ultrasound irradiation at room temperature. The structures of newly synthesized compounds were confirmed through spectral techniques such as IR, H NMR, C NMR, and LCMS. The important features of this protocol include simple and easy workup procedure, reaction carried out at ambient temperature, use of ultrasound and high yield of oxoquinazolin-3(4H)-yl)furan-2-carboxamides in short reaction time.

Synthesis and biological evaluation of 1,2,4-triazolidine-3-thiones as potent acetylcholinesterase inhibitors: in vitro and in silico analysis through kinetics, chemoinformatics and computational approaches.

We have designed and synthesized a novel acidic ionic liquid and explored its catalytic efficiency for the synthesis of 1,2,4-triazolidine-3-thione derivatives. A simple reaction between aldehydes and thiosemicarbazide for short time in 60:40 v/v water/ethanol at room temperature offers target 1,2,4-triazolidine-3-thione derivatives. The formation of target compounds is confirmed by NMR, IR and ESI-MS analysis.

Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies.

Elastase is the only enzyme that has the capability to degrade elastin and collagen, the two proteins essential for skin and bones. The synthesis of some densely substituted piperidines functionalized with the trifluoromethyl group (4a-j) was carried out. The newly prepared compounds were subjected to elastase enzyme inhibitory potential and antioxidant activity assays.

Synthesis, molecular docking and kinetic studies of novel quinolinyl based acyl thioureas as mushroom tyrosinase inhibitors and free radical scavengers.

The enzyme tyrosinase plays a vital role in melanin biosynthesis and enzymatic browning of vegetables and fruits. A series of novel quinolinyl thiourea analogues (11a-j) were synthesized by reaction of 3-aminoquinoline and corresponding isothiocyanates, in moderate to excellent yields with different substitutions and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The compound N-(quinolin-3-ylcarbamothioyl)hexanamide (11c) exhibited the maximum tyrosinase inhibitory effect (IC = 0.

Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics.

A series of symmetrical salicylaldehyde-bishydrazine azo molecules, -, have been synthesized, characterized by H-NMR and C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase.

Metal-Based Scaffolds of Schiff Bases Derived from Naproxen: Synthesis, Antibacterial Activities, and Molecular Docking Studies.

We report here the synthesis, characterization, and antibacterial evaluation of transition metal complexes of Ni, Cu, Co, Mn, Zn, and Cd (⁻), using a Schiff base ligand () derived from naproxen (an anti-inflammatory drug) and 5-bromosalicylaldehyde by a series of reactions. The ligand and the synthesized complexes were characterized by elemental analysis, UV-Visible, FTIR, and XRD techniques. The ligand behaves as a bidentate donor and coordinates with metals in square planar or tetrahedral fashion.

Drug-1,3,4-Thiadiazole Conjugates as Novel Mixed-Type Inhibitors of Acetylcholinesterase: Synthesis, Molecular Docking, Pharmacokinetics, and ADMET Evaluation.

A small library of new drug-1,3,4-thiazidazole hybrid compounds (⁻) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound (IC 18.1 ± 0.

Synthesis of sulfonamide, amide and amine hybrid pharmacophore, an entry of new class of carbonic anhydrase II inhibitors and evaluation of chemo-informatics and binding analysis.

Selective inhibition of carbonic anhydrase (CA) enzyme is an active area of research for medicinal chemists. In the current account, a hybrid pharmacophore approach was employed to design sulfonamide, amide and amine containing new series of potent carbonic anhydrase II inhibitors. The aromatic fragment associated with pharmacophore was altered suitably in order to find effective inhibitors of CA-II.

Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies.

The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis.

Synthesis and structure-activity relationship of tyrosinase inhibiting novel bi-heterocyclic acetamides: Mechanistic insights through enzyme inhibition, kinetics and computational studies.

The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, 9a-n, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as H NMR, C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used.

Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations.

Keeping in mind the pharmacological importance of 2-aminothiazole and 1,2,4-triazole heterocyclic moieties, a series of novel ethylated bi-heterocyclic acetamide hybrids, 9a-p, was synthesized in a multi-step protocol. The structures of newly synthesized compounds were characterized by H NMR, C NMR, IR and EI-MS spectral studies. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against elastase and all these molecules were identified as potent inhibitors relative to the standard used.