Bioorganic and medicinal Chemistry

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Nonconjugated Hydrocarbons as Rigid Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

Nonconjugated Hydrocarbons as Rigid Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

The direct attachment of aryl groups, namely porphyrins onto the cubane core was still a synthetic target for us, so a different approach was sought to achieve this as palladium- catalyzed cross-coupling chemistry failed due to the instability of the cubane core in presence of palladium. A single-electron- transfer mechanism was chosen, as it circumvents the require- ment for the oxidative addition of the transition metal onto the cubane core by instead utilizing the cubyl radical which is rather stable. Moreover, the versatility of redox-active esters used for decarboxylative cubane-aryl cross-coupling had been seen by work performed by the Baran group, which supported SET as a viable method for cubanyl porphyrin coupling. Firstly, optimization of the nickel-catalyzed cubane-aryl coupling was carried out by looking at five major contributing factors: 1) sol- vent, 2) temperature, 3) concentration, 4) Ni source, and 5) ligand. The ligand was identified as the main contributing pa- rameter and results showed that the very electron-deficient 4,4’-functionalized bipyridines, especially the rigid phenanthro-
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Synthesis of some heterocyclic compounds and studies of their antimicrobial efficacy

Synthesis of some heterocyclic compounds and studies of their antimicrobial efficacy

Benzothiazole derivative exhibit a wide range of biological activities[1,2] Benzothiazole moiety exhibits activities such as antiallergic[3], antitumor[4] , antiparstitic, antifungal and antibacterial [5] etc. In bioorganic and medicinal chemistry 2 – aminobenzothiazole derivatives are broadly found with applications in drug discovery and development of the treatments of diabetes[6], epilepsy[7,8], inflammation[9,10], amyotrophic lateral sclerosis[11], analgesic[12], tuberculosis [13] and viral infection[14].

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A study of Fluorine Chemistry at the Multidisciplinary

A study of Fluorine Chemistry at the Multidisciplinary

INTRODUCTION: The extraordinary potential of fluorine-containing biologically relevant molecules in peptide/protein chemistry, medicinal chemistry, chemical biology, pharmacology, drug discovery as well as diagnostic and therapeutic applications was recognized by researchers who are not in the traditional fluorine chemistry field, and thus a new wave of fluorine chemistry has been rapidly expanding its biomedical frontiers. In fact, the importance of fluorine in bioorganic and medicinal chemistry has been demonstrated by a large number of fluorinated
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Synthesis and Invitro Anti-Cancer Evaluation of Some Novel 2, 3 Disubstituted Thiazolidinones

Synthesis and Invitro Anti-Cancer Evaluation of Some Novel 2, 3 Disubstituted Thiazolidinones

Despite the optimal use of available anticancer drugs (ACDs), many patients fail to experience therapeutic efficacy and others do so only at the expense of significant toxic side effects. The limitations with the conventional ACDs highlighted the need for developing newer anti-cancer agents with new, less toxic and more effective drugs are required. Thiazolidinones are five membered ring system containing sulphur and nitrogen atom, received a much attention of medicinal chemists due to their potential biological activities. Various substituents’ at C-2 and C-3 of thiazolidinone results in potent anticancer activity. Prompted by these reports, we aimed to prepare the following series of 2, 3-disubstituted- Thiazolidinone derivatives as potent anticancer agents.
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Studies of the Interaction of Au(I)-Phosphole Complexes with DNA and their Relation to Biological Activity

Studies of the Interaction of Au(I)-Phosphole Complexes with DNA and their Relation to Biological Activity

Metal complexes have gained considerable interest in both the development and the treatment of cancer. For example, platinum compounds are well established in current cancer [1]. Cisplatin is one of the most widely used metal-based antitumor drugs targeting DNA. Although it is active in the treatment of several types of cancers, the side-effects limit its potential efficacy [2,3]. Consequently, there is a considerable need for the development of novel metallo drugs and treatment alternatives. Among the new non-platinum drugs especially gold complexes have been focus of attention due to their strong tumor cell growth inhibiting effects, showing unique biological and medicinal properties [4,5]. Particularly, Au(I) phosphine complexes have shown great potential as anticancer agents, however, their efficacy has been limited by their high toxicity and lack of selectivity for cancer cells [6].
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COMPUTER-ASSISTED CLASSES ON MEDICINAL CHEMISTRY OF NEUROLEPTICS

COMPUTER-ASSISTED CLASSES ON MEDICINAL CHEMISTRY OF NEUROLEPTICS

to bridge this gap, several computer-assisted classes on medicinal chemistry have been elaborated (muranaka, 2001; Kossida, tahri & daizadeh, 2002; tavares de oliveira et al., 2006; persona et al., 2007; tsai, 2007; Kaczor, matosiuk & persona, 2009a, 2009b, 2009c; persona et al., 2009; persona et al., 2010). these classes involve teaching protein science with application of computers, conformational analysis of natural ligands and molecular docking studies, molecular modeling and calculation of the structure-correlated parameters describing skin permeability of theaflavonoids, structure-activity studies, structure-based virtual screening for novel monoaminooxidase b (mao-b) inhibitors and estimation of drug-likeness and calculation of admet properties for some series of novel compounds. the students who participated in the classes respond positively or even enthusiastically to the above computer- assisted classes on medicinal chemistry and highly approved such an educational approach. thus, it was an encouragement and motivation to design subsequent computer-assisted classes on this branch of science.
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Biotransformations in Drug Synthesis: A Green and Powerful Tool for Medicinal Chemistry

Biotransformations in Drug Synthesis: A Green and Powerful Tool for Medicinal Chemistry

Hence, the first step involves the biocatalytic reduction of 8, using a genetically improved keto reductase (KRED) in combination with a modified NADP-dependent glucose dehydrogenase (GDH) for cofactor regeneration, leading to 9 in 96% isolated yield and >99.5% ee. In the second step, a halohydrin dehalogenase (HHDH), an enzyme capable of catalysing the elimination of halides from vicinal haloalcohols, resulting in epoxide ring formation [78], also catalytically enhanced by directed evolution, was employed to catalyse the nucleophilic substitution of chloride by cyanide. The efficiency and greenness of this protocol (Codexis was awarded the U.S. Environmental Protection Agency’s Presidential Green Chemistry Challenge Award in 2006 for this work [79] is based on the fact that all previous manufacturing routes to HN involved, as the final step, a standard but troublesome S N 2 substitution of halide with cyanide ion in alkaline solution (pH=10) at high temperatures (80ºC), being this reaction substituted in the Codexis protocol [40]. In fact, in the S N 2 chlorine substitution, both 9 and 10 are base-sensitive molecules, and extensive by-product formation is observed, leading to high E values [77]. Moreover, the product is a high-boiling oil, and a troublesome high-vacuum fractional distillation is required to recover 10, resulting in further yield losses and waste, and clearly contravening the 1 st
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Synthesis, Antimicrobial, Antioxidant and Molecular Docking Study of Some Novel Bis-1, 2, 4-Triazolo [3, 4-b]-1, 3, 4-Thiadiazoles

Synthesis, Antimicrobial, Antioxidant and Molecular Docking Study of Some Novel Bis-1, 2, 4-Triazolo [3, 4-b]-1, 3, 4-Thiadiazoles

The synthesized compounds showed DPPH scavenging activity varying from 76.38±0.32% to 18.01±0.15%, whereas standard drug BHA showed 88.33±0.33% inhibition.. The newly synthesized comp[r]

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Synthesis, Characterization and Antimicrobial Activity of Schiff Base (E) N (4 (2 Hydroxybenzylideneamino) Phenylsulfonyl) Acetamide Metal Complexes

Synthesis, Characterization and Antimicrobial Activity of Schiff Base (E) N (4 (2 Hydroxybenzylideneamino) Phenylsulfonyl) Acetamide Metal Complexes

reported showing its versatility in coordination chemistry and medicinal chemistry, for examples, cobalt(II), copper(II), nickel(II) and zinc(II) complexes of mercaptothiadiazole-derived from furanyl, thienyl, pyrrolyl, sa- licylyl and pyridinyl Schiff bases [10], anti-tuberculosis agent and pharmacological activities of sulfonamide copper complexes [11], crystal structure of zinc(II) 2-sulfanilamidopyrimidine [12], sulfamethoxydiazine com- plexes of copper(II), zinc(II), nickel(II), cadmium(II), chromium(III) and iron(III) [13], disulfamethoxazole di- aquo Ni(II) monohydrate [14], Copper complexes with sulfonamides with pUC18 plasmid and hydrogen perox- ide [15], binuclear dioxomolybdenum(VI) chelates involving Schiff bases derived from sulpha drugs and 4- benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one [16], sulfa oxovanadium(IV) complexes involving the O,N-do- nor environment of pyrazolone-based drug Schiff bases [17], mixed ligand complexes of Cu(II), Ni(II), Co(II), Zn(II), Sm(III), and UO 2 (VI) with a Schiff Base derived from the sulfamerazine and 2,2′-bipyridine [18]. Cur-
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Reactive Oxygen Species and their Interaction with Platelets

Reactive Oxygen Species and their Interaction with Platelets

During trauma, the formation of ROS/RNS leads to direct endothelial damage and elevates the concentration of potent platelet activators such as thrombin. Under increased oxidative stre[r]

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A Review on Anti-Cholesterol Drugs and their Mechanisms

A Review on Anti-Cholesterol Drugs and their Mechanisms

CETP inhibitors: Cholesteryl ester transfer protein (CETP) promotes transfer of cholestyeryl esters from HDLs to other lipoprotein. By inhibiting CETP increase HDL-C eventually decre[r]

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In vitro antimicrobial and α-glucosidase inhibitory potential of enantiopure cycloalkylglycine derivatives: Insights into their in silico pharmacokinetic, druglikeness, and medicinal chemistry properties

In vitro antimicrobial and α-glucosidase inhibitory potential of enantiopure cycloalkylglycine derivatives: Insights into their in silico pharmacokinetic, druglikeness, and medicinal chemistry properties

The pharmacokinetic and druglikeness properties of the synthesized drugs, such as passive human gastrointestinal absorption (GI), blood–brain barrier (BBB) permeation, skin penetration coefficient, substrate or non-substrate of the permeability glycoprotein (P-gp), and interaction of molecules with five major isoforms of the human cytochromes P450 interfering in the metabolism of numerous endogenous and exogenous compounds, have been predicted using SwissADME online server (http://www.swissadme.ch/) (Daina et al., 2017). Furthermore, the medicinal chemistry characteristics such as PAINS for pan-assay interference compounds or promiscuous compounds, Brenk alert which inform about allegedly toxic, metabolically unstable, chemically reactive fragments present in the structure, and leadlikeness and synthetic accessibility
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One pot synthesis and antibacterial activity of substituted benzothiazolylacetamide

One pot synthesis and antibacterial activity of substituted benzothiazolylacetamide

Benzothiazole derivatives are an important class of heterocyclic compounds that exhibit a wide range of biological properties in medicinal and agricultural chemistry 1-5 . Further industrial applications as antioxidants, vulcanization accelerators and a dopant in a light emitting organic electroluminescent devices 6 have also been reported. Many reports have appeared in the literature describing the formation of benzothiazoles via one of the two major routes. The most commonly used method involves the condensation of o-aminothiophenols with substituted nitriles, aldehydes, carboxylic acids, acyl chlorides, or esters in the presence of a catalyst such as p-toluenesulfonic acid (PTSA) in an organic solvent 7-14 . Another route is based on oxidative cyclization of thiobenzanilides using various oxidants 15 .
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One pot Synthesis and Antibacterial Activity of Substituted Benzothiazolyl Acetamide

One pot Synthesis and Antibacterial Activity of Substituted Benzothiazolyl Acetamide

Benzothiazole derivatives are an important class of heterocyclic compounds that exhibit a wide range of biological properties in medicinal and agricultural chemistry 1-5 . Further industrial applications as antioxidants, vulcanization accelerators and a dopant in a light emitting organic electroluminescent devices 6 have also been reported. Many reports have appeared in the literature describing the formation of benzothiazoles via one of the two major routes. The most commonly used method involves the condensation of o-aminothiophenols with substituted nitriles, aldehydes, carboxylic acids, acyl chlorides, or esters in the presence of a catalyst such as p-toluenesulfonic acid (PTSA) in an organic solvent 7-14 . Another route is based on oxidative cyclization of thiobenzanilides using various oxidants 15 .
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Fundamentals of Medicinal Chemistry (2003) By Gareth Thomas pdf

Fundamentals of Medicinal Chemistry (2003) By Gareth Thomas pdf

where r is the position of the electron. The use of the Hartree–Fock approxima- tion reduces computer time and reduces the cost without losing too much in the way of accuracy. Computer time may be further reduced by the use of semi- empirical methods. These methods use experimentally determined data to sim- plify many of the atomic orbitals, which in turn simplifies the Schrodinger equation for the structure. Solving the Schrodinger equation uses a mathemat- ical method, which is initially based on guessing a solution for each electrons molecular orbital. The computer tests the accuracy of this trial solution and based on its findings modifies the trial solution to produce a new solution. The accuracy of this new solution is tested and a further solution is proposed by the computer. This process is repeated until the testing the solution gives answers within acceptable limits. In molecular modelling the solutions obtained by the use of these methods describe the molecular orbitals of each electron in the molecule. The solutions are normally in the form of sets of equations, which may be interpretated in terms of the probability of finding an electron at specific points in the structure. Graphics programs may be used to convert these prob- abilities into either presentations like those shown in Figures 5.1 and 5.2 or into electron distribution pictures (Figure 5.8). However, because of the computer time involved, it is not feasible to deal with structures with more than several hundred atoms, which makes the quantum mechanical approach less suitable for large molecules such as the proteins that are of interest to medicinal chemists.
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THIOSEMICARBAZONE COMPLEXES AS VERSATILE MEDICINAL CHEMISTRY AGENTS: A REVIEW

THIOSEMICARBAZONE COMPLEXES AS VERSATILE MEDICINAL CHEMISTRY AGENTS: A REVIEW

Schiff bases are important organic ligands having potential tendency of complexation with transition metals and they have shown excellent pharmacological properties over the years. Thiosemicarbazones are well known Schiff based ligands which are usually neutral yet their anioninc forms are also known. Their bidentate, tridentate or in some cases polydentate nature is due to the presence of donor atoms like sulphur, nitrogen or in some instances oxygen. As transition metals can exhibit an array of coordination power, they easily form stable complexes with Schiff based thiosemicarbazone ligands. Latest advances in medicinal inorganic chemistry have given considerable importance to the development of metal based drugs. Since the presence of metal ion in the drug moiety usually mitigates the ill effects of carbon-based compounds, this may lead to the production of new metal based drugs. The key factors identified for their action has been the inhibition of RR, topo II and the production of ROS, but identification of other probable targets need to be explored. The main action of the metal chelates when compared to free ligand is the prevalence of diffusive mechanism over the active transport mechanism across the membrane. The chelation of the metal ion by the polar regions of the ligands facilitates easy uptake by the cell. Just a limited number of in vivo studies have been done indicating the need of further deliberations. Attempts have been made to enhance the hydrophilicity and decrease the side effects of the parent moiety by suitable modifications in the thiosemicarbazone frameworks. Another area which needs attention is metal ion sequestering, as thiosemicarbazones are versatile chelators, they sometimes deprive the cell of essential metal ions by forming stable chelates with them
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COUMARIN AS A VERSATILE SYNTHON IN MEDICINAL CHEMISTRY

COUMARIN AS A VERSATILE SYNTHON IN MEDICINAL CHEMISTRY

Synthesis, biological evaluation and molecular docking of novel Chalcone coumarin hybrids as anticancer and antimalarial agents. Synthesis and biological evaluation of[r]

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PYRAZOLES IN MEDICINAL CHEMISTRY

PYRAZOLES IN MEDICINAL CHEMISTRY

A possible mechanistic pathway for change in the site of nucleophilic attack due to the CF3 group in 2(1H) pyridones is described. 2-Formyl glycals undergo rapid condensation with aryl[r]

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The Journal of Computer-Aided Molecular Design: a bibliometric note

The Journal of Computer-Aided Molecular Design: a bibliometric note

The editorial of the very first issue of the Journal of Computer-Aided Molecular Design (hereafter JCAMD) stated that “a new discipline has emerged which has invaded almost all aspects of the study of molecular structure and recognition. Its applications range through modern medicinal chemistry, protein engineering, catalytic design, polymer studies and many other facets of organic, inorganic, physical and biological chemistry” [1]. The journal was established to provide a mechanism for research findings in this new discipline, and it has done this with conspicuous success for a quarter of a century. The first volume appeared in 1987 with this and the subsequent three volumes all containing four issues. The journal moved to having six issues a volume in 1991, to eight in 2000, and to its current monthly publication in the following year following its merger with the closely related review journal Perspectives in Drug Discovery and Design. The steady growth in the number of issues (and, consequently, in the number of articles, with 22 in the first volume and 91 in the most recently completed volume for 2010) demonstrates that the journal is successfully meeting the needs of an increasingly widespread academic community.
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Synthesis and in Vitro Cytotoxic Activity of Novel  Pyrazole 3,4 dicarboxylates

Synthesis and in Vitro Cytotoxic Activity of Novel Pyrazole 3,4 dicarboxylates

Pyrazole and its derivatives, occupy an important posi- tion in medicinal chemistry with a wide range of bioac- tivities. They possess anti-obesity [1], receptor antago- nists [2], HIV reverse transcriptase inhibitors [3], and anti-hyperglycemic activities [4]. They are also used as anti-inflammatory [5,6], antipyretic [7], antiarrhythmic [8], antitumor [9,10], monoamine oxidase inhibiting [11] and antibacterial agents [12]. Considering the important bio- logical properties of pyrazole compounds, numerous methods toward pyrazoles syntheses have been devel- oped over the past decades [13-17]. Despite numerous di- verse approaches toward syntheses of pyrazoles devel- oped so far, it is still challenging to prepare polysubsti- tuted pyrazoles with various substituents from readily available building blocks. Herein we report a facile ap- proach to provide polysubstituted pyrazoles via 1,3-di- polar cycloaddition of ethyl cyanoacetate with N-Aryl-C- ethoxycarbonylnitrile imines. Evaluation of their cyto- toxic activity toward cell line P815 is reported.
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