New Biological Targets for the Treatment of Leishmaniasis

: Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations. Type III receptor tyrosine kinase affects most of the fundamental cellular processes including cell cycle, cell migration, cell metabolism, and survival, as well as cell proliferation and differentiation. Many inhibitors of successful rational drug design show that some computational techniques can be combined to achieve synergistic effects.

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Identification of Antineoplastic Targets with Systems Approaches, Using Resveratrol as an In-Depth Case Study

Current Pharmaceutical Design ◽

10.2174/1381612823666170710152918 ◽

2017 ◽

Vol 23 (32) ◽

pp. 4773-4793 ◽

Cited By ~ 5

Author(s):

Nivedita Singh ◽

Sherry Freiesleben ◽

Olaf Wolkenhauer ◽

Yogeshwer Shukla ◽

Shailendra K. Gupta

Keyword(s):

Drug Target ◽

Complex Disease ◽

Biological Targets ◽

Systems Approaches ◽

Anticancer Mechanism ◽

Genetic And Environmental Factors ◽

Key Steps ◽

Network Approaches ◽

Novel Drug

The identification and validation of novel drug–target combinations are key steps in the drug discovery processes. Cancer is a complex disease that involves several genetic and environmental factors. High-throughput omics technologies are now widely available, however the integration of multi-omics data to identify viable anticancer drug-target combinations, that allow for a better clinical outcome when considering the efficacy-toxicity spectrum, is challenging. This review article provides an overview of systems approaches which help to integrate a broad spectrum of technologies and data. We focus on network approaches and investigate anticancer mechanism and biological targets of resveratrol using reverse pharmacophore mapping as an in-depth case study. The results of this case study demonstrate the use of systems approaches for a better understanding of the behavior of small molecule inhibitors in receptor binding sites. The presented network analysis approach helps in formulating hypotheses and provides mechanistic insights of resveratrol in neoplastic transformations.

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Synthetic Routes for 1,4-disubstituted 1,2,3-triazoles: A Review

Current Organic Chemistry ◽

10.2174/1385272823666190514074146 ◽

2019 ◽

Vol 23 (8) ◽

pp. 860-900 ◽

Cited By ~ 8

Author(s):

Chander P. Kaushik ◽

Jyoti Sangwan ◽

Raj Luxmi ◽

Krishan Kumar ◽

Ashima Pahwa

Keyword(s):

Solid Phase ◽

Click Reaction ◽

Biological Activities ◽

Triazole Ring ◽

Copper Catalysts ◽

Biologically Active ◽

Pharmaceutical Chemistry ◽

Biological Targets ◽

Synthetic Routes ◽

High Yields

N-Heterocyclic compounds like 1,2,3-triazoles serve as a key scaffolds among organic compounds having diverse applications in the field of drug discovery, bioconjugation, material science, liquid crystals, pharmaceutical chemistry and solid phase organic synthesis. Various drugs containing 1,2,3-triazole ring which are commonly available in market includes Rufinamide, Cefatrizine, Tazobactam etc., Stability to acidic/basic hydrolysis along with significant dipole moment support triazole moiety for appreciable participation in hydrogen bonding and dipole-dipole interactions with biological targets. Huisgen 1,3-dipolar azide-alkyne cycloaddition culminate into a mixture of 1,4 and 1,5- disubstituted 1,2,3-triazoles. In 2001, Sharpless and Meldal came across with a copper(I) catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles by cycloaddition between azides and terminal alkynes. This azide-alkyne cycloaddition has been labelled as a one of the important key click reaction. Click synthesis describes chemical reactions that are simple to perform, gives high selectivity, wide in scope, fast reaction rate and high yields. Click reactions are not single specific reaction, but serve as a pathway for construction of simple to complex molecules from a variety of starting materials. In the last few decades, 1,2,3-triazoles attracted attention of researchers all over the world because of their broad spectrum of biological activities. Keeping in view the biological importance of 1,2,3-triazole, in this review we focus on the various synthetic routes for the syntheisis of 1,4-disubstituted 1,2,3-triazoles. This review involves various synthetic protocols which involves copper and non-copper catalysts, different solvents as well as substrates. It will boost synthetic chemists to explore new pathway for the development of newer biologically active 1,2,3-triazoles.

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Coumarin Hybrids: Promising Scaffolds in the Treatment of Breast Cancer

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190308122509 ◽

2019 ◽

Vol 19 (17) ◽

pp. 1443-1458 ◽

Cited By ~ 2

Author(s):

Rohit Bhatia ◽

Ravindra K. Rawal

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Therapeutic Agents ◽

Toxicity Profile ◽

Biological Targets ◽

Organ Systems ◽

Hybrid Molecules ◽

Cause Of Deaths ◽

Low Toxicity ◽

Diverse Mode

: Breast cancer is the most common invasive cancer in women, and the second main cause of deaths in women, after lung cancer. There is continuous advancement in the development of therapeutic agents against breast cancer in recent years and it is still in progress. Development of hybrid molecules by combining different pharmacophores to obtain significant biological activity is an excellent approach. Coupling of coumarin scaffold with other distinct motifs has led to the design of newer compounds against breast cancer. These distinct pharmacophores possess a diverse mode of action as well as selectivity. It has been reported in the literature that coumarin hybrids possess significant potency against breast cancer by binding to various biological targets which are associated with breast cancer. Due to low toxicity profile on various organ systems, coumarin hybrids have nowadays attracted the keen attention of researchers to explore their therapeutic ability against breast cancer. Reported coumarin hybrids include coupling with isoxazole, thiazole, monastrol, chalcone, triazole, sulphonamide, triphenylethylene, benzimidazole, pyran, imidazole, stilbene, oestrogen, phenylsulphonylfuroxan, etc. In the present review, a description of various coumarin hybrid molecules has been presented along with their structural-activity relationships.

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Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

Current Organic Synthesis ◽

10.2174/1570179415666171206151603 ◽

2018 ◽

Vol 15 (2) ◽

pp. 208-220 ◽

Cited By ~ 3

Author(s):

Vaibhav Mishra ◽

Tejpal Singh Chundawat

Keyword(s):

Bond Formation ◽

Catalyst Design ◽

Biologically Active ◽

Reaction Conditions ◽

Biological Targets ◽

Amination Reaction ◽

Drug Synthesis ◽

Substituted Piperazine ◽

Approved Drugs ◽

Fda Approved Drugs

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

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Secondary Metabolites of Plant Origin containing Carbazole as Lead Molecule: A Review

Current Traditional Medicine ◽

10.2174/2215083805666190617110019 ◽

2019 ◽

Vol 05 ◽

Author(s):

Atul Sharma ◽

Devender Pathak

Keyword(s):

Drug Discovery ◽

Heterocyclic Compounds ◽

Biological Activities ◽

Chemical Compounds ◽

Lethal Effect ◽

Chemical Diversity ◽

Chemical Transformations ◽

Pharmacological Effects ◽

Structural Class ◽

Biological Targets

Keeping this fact that study of a body is biology but life is all about chemicals and chemical transformations, many medicinal chemist start research in finding new and novel chemical compounds which having pharmacological activities. Most of those chemical compounds which are having active pharmacological effects are heterocyclic compounds. Heterocyclic compounds clutch a particular place among pharmaceutically active natural and synthetic compounds. The ability to serve both as biomimetics and reactive pharmacophores of heterocyclic nuclei is incredible and it has principally contributed to their unique value as traditional key elements of numerous drugs. These heterocyclic nuclei offer a huge area for new lead molecules for drug discovery and for generation of activity relationships with biological targets to enhance pharmacological effects. For these reasons, it is not surprising that this structural class has received special attention in drug discovery. The hydrogen bond acceptors and donors arranged in a manner of a semi-rigid skeleton in heterocyclic rings and therefore they can present a varied display of significant pharmacophores. Lead identification and optimization of drug target probable can be achieved by generation of chemical diversity produced by derivatization of heterocyclic pharmacophores with different groups or substituents. A tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various potential biological activities such as anticancer, antimicrobial and antiviral. Binding mechanism of carbazole with target receptor as a molecule or fused molecule exhibits the potential lethal effect.

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Chemical conjugation of nucleic acid aptamers and synthetic polymers

Polymer Chemistry ◽

10.1039/d1py00516b ◽

2021 ◽

Author(s):

Maria Nerantzaki ◽

Capucine Loth ◽

Jean-Francois Lutz

Keyword(s):

Nucleic Acid ◽

Synthetic Polymers ◽

Specific Sequence ◽

Biological Targets ◽

Nucleic Acid Aptamers ◽

Chemical Conjugation ◽

Sequence Dependent

Nucleic acid aptamers are chemically-synthesized single-stranded oligonucleotides that fold into specific sequence-dependent configurations. Due to their exceptional recognition properties towards a variety of biological targets, they find applications in many...

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Ten years of molecular ballistics—a review and a field guide

International Journal of Legal Medicine ◽

10.1007/s00414-021-02523-0 ◽

2021 ◽

Author(s):

Jan Euteneuer ◽

Cornelius Courts

Keyword(s):

Model Building ◽

Crime Scene ◽

Forensic Evidence ◽

Biological Targets ◽

Contrast Method ◽

History Of ◽

Scene Investigation ◽

Blood Pattern Analysis ◽

Wound Ballistic ◽

Objective Investigation

AbstractMolecular ballistics combines molecular biological, forensic ballistic, and wound ballistic insights and approaches in the description, collection, objective investigation, and contextualization of the complex patterns of biological evidence that are generated by gunshots at biological targets. Setting out in 2010 with two seminal publications proving the principle that DNA from backspatter collected from inside surfaces of firearms can be retreived and successfully be analyzed, molecular ballistics covered a lot of ground until today. In this review, 10 years later, we begin with a comprehensive description and brief history of the field and lay out its intersections with other forensic disciplines like wound ballistics, forensic molecular biology, blood pattern analysis, and crime scene investigation. In an application guide section, we aim to raise consciousness to backspatter traces and the inside surfaces of firearms as sources of forensic evidence. Covering crime scene practical as well as forensic genetic aspects, we introduce operational requirements and lay out possible procedures, including forensic RNA analysis, when searching for, collecting, analyzing, and contextualizing such trace material. We discuss the intricacies and rationales of ballistic model building, employing different tissue, skin, and bone simulants and the advantages of the “triple-contrast” method in molecular ballistics and give advice on how to stage experimental shootings in molecular ballistic research. Finally, we take a look at future applications and prospects of molecular ballistics.

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Biosynthesis of Nature-Inspired Unnatural Cannabinoids

Molecules ◽

10.3390/molecules26102914 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2914

Author(s):

Kevin J. H. Lim ◽

Yan Ping Lim ◽

Yossa D. Hartono ◽

Maybelle K. Go ◽

Hao Fan ◽

...

Keyword(s):

Synthetic Biology ◽

Cannabis Sativa ◽

Genetic Manipulation ◽

Therapeutic Agents ◽

Orphan Receptors ◽

Complex Chemical ◽

Biological Targets ◽

Chemical Structures ◽

Commercial Use ◽

Wide Range

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.

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Application of Cryo-Electron Microscopy on Drug Discovery

Microscopy and Microanalysis ◽

10.1017/s143192762101120x ◽

2021 ◽

Vol 27 (S1) ◽

pp. 3250-3250

Author(s):

Viswanath Vittaladevaram ◽

Kranthi Kuruti

Keyword(s):

Electron Microscopy ◽

Protein Complexes ◽

Lead Discovery ◽

Biologically Relevant ◽

Biological Targets ◽

3 Dimensional ◽

Drug Molecules ◽

Cryo Electron Microscopy ◽

Therapeutic Molecules ◽

Novel Drug

AbstractThe key aspect for development of novel drug molecules is to perform structural determination of target molecule associated with its ligand. One such tool that provides insights towards structure of molecule is Cryo-electron microscopy which covers biological targets that are intractable. Examination of proteins can be carried out in native state, as the samples are frozen at -175 degree Celsius i.e. cryogenic temperatures. In addition to this, there were no limits for molecular and functional structures of proteins that can be imagined in 3-dimensional form. This includes ligands which unravel mechanisms that are biologically relevant. This will enable to better understand the mechanisms that are used for development of new therapeutics. Application of Cryo-electron microscopy is not limited to protein complexes and is considered as non-specific. Intervention of Cryo-EM would allow to analyse the structures and also able to dissect the interaction with therapeutic molecules. The study determines the usage of cryo-EM for providing resolutions that are acceptable for lead discovery. It also provides support for lead optimization and also for discovery of vaccines and therapeutics.

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