3D-QSAR, Pharmacophore Modeling, ADMET, and DFT Studies of Halogenated Conjugated Dienones as Potent MAO-B Inhibitors.

Introduction: It has been reported that the extension of conjugation in chalcone scaffolds considerably enhanced the potency, selectivity, reversibility, and competitive mode of MAO-B inhibition. In this study, using the experimental results of IC50 values of fifteen halogenated conjugated dienone derivatives (MK1-MK15) against MAO-B, we developed a 3DQSAR model.

Methods: Further, we created a 3D pharmacophore model in active compounds in the series.

Advancements in COVID-19 Testing: An In-depth Overview.

COVID-19 rapidly evolved as a pandemic, killing and hospitalising millions of people, and creating unprecedented hurdles for communities and health care systems worldwide. The rapidly evolving pandemic prompted the head of the World Health Organisation to deliver a critical message: "test, test, test." The response from the diagnostic industry and researchers worldwide was overwhelming, resulting in more than a thousand commercial tests being available worldwide.

Biological investigation of -methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors.

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases.

Replacement of Chalcone-Ethers with Chalcone-Thioethers as Potent and Highly Selective Monoamine Oxidase-B Inhibitors and Their Protein-Ligand Interactions.

To develop new potent and highly selective MAO-B inhibitors from chalcone-thioethers, eleven chalcones-thioethers were synthesized and their monoamine oxidase (MAO) inhibition, kinetics, reversibility, and cytotoxicity of lead compounds were analyzed. Molecular dynamics were carried out to investigate the interactions. Compound showed potent inhibitory activity against MAO-B, with an IC value of 0.

COVID-19 and Domestic Animals: Exploring the Species Barrier Crossing, Zoonotic and Reverse Zoonotic Transmission of SARS-CoV-2.

Background: To date, more than thirty animals have been tested positive for SARS-CoV-2; all of them infected by humans with COVID-19. Some animal experiments suggested the possibility of animal to animal transmission of SARS-CoV-2 that was seen in some cases of infected animals. Animal to human transmission was considered unlikely until investigations revealed the possibility of mink to human transmission of SARS-CoV-2 in the Netherlands.

The Chronicle of COVID-19 and Possible Strategies to Curb the Pandemic.

COVID-19, a type of infection that emerged in Wuhan, has become a pandemic affecting people worldwide and is rapidly spreading and evolving. Day by day, the confirmed cases and deaths are increasing many folds. SARS-CoV-2 is a novel virus; therefore, limited data are available to curb the disease.

Development of methylthiosemicarbazones as new reversible monoamine oxidase-B inhibitors for the treatment of Parkinson's disease.

Selective monoamine oxidase-B (MAO-B) inhibition is an attractive subject for the treatment of Parkinson's disease (PD). In the current study, we synthesized some selected derivatives of methylthiosemicarbazones and investigated their MAOs and acetylcholinesterase (AChE) inhibitory activities. Among the series synthesized, compounds , , and most inhibited MAO-B with IC values of 5.

Fascinating Chemopreventive Story of Wogonin: A Chance to Hit on the Head in Cancer Treatment.

Cancer, global havoc, is a group of debilitating diseases that strikes family as well as society. Cancer cases are drastically increasing these days. Despite many therapies and surgical procedures available, cancer is still difficult to control due to limited effective therapies or targeted therapies.

Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules.

Barriers are the hallmark of a healthy physiology, blood-brain barrier (BBB) being a tough nut to crack for most of the antigens and chemical substances. The presence of tight junctions plays a remarkable role in defending the brain from antigenic and pathogenic attacks. BBB constitutes a diverse assemblage of multiple physical and chemical barriers that judiciously restrict the flux of blood solutes into and out of the brain.

Magnetic nanoparticles for hyperthermia in cancer treatment: an emerging tool.

Cancer remains as the major cause of death worldwide. The main reason why available therapies fail is that a vicious cycle in established which initiates multiple pathways and recurrence after metastasis. Hyperthermic treatment, which involves heating tumor tissues to a moderate temperature of 40-43 °C, has emerged as an effective strategy for treating tumors.

Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases.

No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally. On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach.

Advancements in nanotherapeutics for Alzheimer's disease: current perspectives.

Objectives Considerable progress has been made in the treatment of Alzheimer's disease (AD), but all available strategies focus on alleviating symptoms rather than curing, which means that AD is viewed as an unresolvable neurodegenerative disease. Nanotechnological applications offer an alternative platform for the treatment of neurodegenerative diseases. This review aims to summarize the recent nanomedicine and nanotechnology developments for the treatment of AD.

Perspective Design of Chalcones for the Management of CNS Disorders: A Mini-Review.

The development of chalcone-based compounds for CNS disorders has been explored by many research groups. Chalcones are being considered as a potent organic scaffold with widespread applications in the field of drug discovery and medicinal chemistry. The planar or semi-planar geometry of chalcones with various functionalities impinged on the terminal aromatic systems renders the molecule its bio-activity including anti-cancer, anti-malarial, anti-microbial, anti-fungal, antileishmanial, anti-viral, anti-diabetic, anti-hypertensive properties, etc.

Potent and highly selective dual-targeting monoamine oxidase-B inhibitors: Fluorinated chalcones of morpholine versus imidazole.

Two series of fluorinated chalcones containing morpholine and imidazole-based compounds (f1-f8) were synthesized and evaluated for recombinant human monoamine oxidase (MAO)-A and -B as well as acetylcholinesterase inhibitory activities. Our results indicate that morpholine containing chalcones are highly selective MAO-B inhibitors having reversibility properties. All the imidazole-based fluorinated chalcones showed weak MAO inhibitions in both isoforms.

Selected aryl thiosemicarbazones as a new class of multi-targeted monoamine oxidase inhibitors.

A series of 13 phenyl substituted thiosemicarbazones () were synthesized and evaluated for their inhibitory potential towards human recombinant monoamine oxidase A and B (MAO-A and MAO-B, respectively) and acetylcholinesterase. The solid state structure of was ascertained by the single X-ray diffraction technique. Compounds and were potent for MAO-A (IC 1.

Fe O nanoparticles mediated synthesis of novel spirooxindole-dihydropyrimidinone molecules as Hsp90 inhibitors.

Heat shock protein 90 (Hsp90) is a validated molecular chaperone considered as the new key recipient for cancer intervention. The current study illustrates the synthesis of novel spirooxindole-dihydropyrimidinones (4a-j) by Fe O nanoparticles intervened synthesis and their Hsp90 ATPase inhibitory activity was investigated by the malachite green assay. All the compounds in the study demonstrated a moderate to potent ATPase inhibitory profile, with IC values ranging from 0.

Cholinesterase Inhibitory Activities of Selected Halogenated Thiophene Chalcones.

Background: Dual-acting human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) inhibitors are more effective than the classic one-drug one-target therapy for Alzheimer's disease (AD).

Methods: The ChE inhibitory ability of some halogenated thiophene chalcone-based molecules known to be selective hMAO-B inhibitors was evaluated.

Results: Based on the IC50 values, the selected compounds were found to moderately inhibit ChE, with IC50 values in the range of 14-70 µM.

Monoamine oxidase inhibitory activity of methoxy-substituted chalcones.

The MAO-B inhibitory activity of chalcone (1, 3- diphenyl-2-propen-1-one) based compounds arise from its structural similarity with 1, 4-diphenyl-2-butene, a known MAO-B inhibitor. Based on our previous report, the methoxy-substituted with fluorine containing chalcones are promising reversible MAO-B inhibitors, while in the present study, a series of methoxylated chalcones (C1-C9) bearing substitution on the para position of ring B was synthesized and evaluated for their human monoamine oxidase inhibitory activity. With the exception of (2E)-1-(4-methoxyphenyl)-3-(4-nitrophenyl) prop-2-en-1-one (C7), which is a nonselective inhibitor, the chalcones exhibited competitive, selective, and reversible inhibition of hMAO-B.

Structural Exploration of Synthetic Chromones as Selective MAO-B Inhibitors: A Mini Review.

Aim And Objective: Specific inhibitors of monoamine oxidase (MAO)-B are considered useful therapeutic agents in targeting neurological disorders like Alzheimer's and Parkinson's diseases. Due to the academic challenge of designing new hMAO-B inhibitors and the possibility of discovering compounds with improved properties compared to existing MAO-B inhibitors, a number of research groups are searching for new classes of chemical compounds that may act as selective hMAO-B inhibitors.

Materials And Methods: Among these, chromone (4H-1-benzopyran-4-one) derivatives have recently emerged as a chemotype with specific and high potency MAO-B inhibition.

Pharmacophore-Based 3D-QSAR Analysis of Thienyl Chalcones as a New Class of Human MAO-B Inhibitors: Investigation of Combined Quantum Chemical and Molecular Dynamics Approach.

Selective monoamine oxidase-B (MAO-B) inhibitors are imperative in the treatment of various neurodegenerative disorders. Herein, we describe the pharmacophore generation and atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses of previously reported thiophene-based hMAO-B inhibitors by our research group. The aim of this study was to identify the principal structural features that could potentially be responsible for the inhibitory activity of hMAO-B inhibitors.

Monoamine Oxidase Inhibitory Activity: Methyl- versus Chlorochalcone Derivatives.

Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO-B except (2E)-1-(4-methylphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P7) and (2E)-1-(4-chlorophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P17), which were found to be selective inhibitors of hMAO-A.

Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives.

For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO.

Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors.

Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B.

Synthesis, Biochemistry, and Computational Studies of Brominated Thienyl Chalcones: A New Class of Reversible MAO-B Inhibitors.

A series of (2E)-1-(5-bromothiophen-2-yl)-3-(para-substituted phenyl)prop-2-en-1-ones (TB1-TB11) was synthesized and tested for inhibitory activity toward human monoamine oxidase (hMAO). All compounds were found to be competitive, selective, and reversible toward hMAO-B except (2E)-1-(5-bromothiophen-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TB7) and (2E)-1-(5-bromothiophen-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one (TB8), which were selective inhibitors of hMAO-A. The most potent compound, (2E)-1-(5-bromothiophen-2-yl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one (TB5), showed the best inhibitory activity and higher selectivity toward hMAO-B, with Ki and SI values of 0.

Ligand based drug design of new heterocyclic imines of GABA analogues: A molecular docking approach for the discovery of new GABA-AT inhibitors.

Background: Degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is mainly catalysed by GABA aminotransferase (GABA-AT), excessive activity of which leads to convulsions. Inhibition of GABA-AT increases the concentration of GABA and can terminate the convulsions. Several studies have revealed that GABA analogues could be the outstanding scaffolds for the design of potent inhibitors of GABA-AT.