scholarly journals Advances of Benzimidazole Derivatives as Anticancer Agents: Bench to Bedside

2022 ◽  
Author(s):  
Kashif Haider ◽  
Mohammad Shahar Yar
Keyword(s):  
Cancer Research ◽  
Biological Activity ◽  
Anticancer Drugs ◽  
Broad Spectrum ◽  
Anticancer Agents ◽  
Therapeutic Potential ◽  
Structural Features ◽  
Clinical Development ◽  
Benzimidazole Derivatives ◽  
Antimitotic Agent

Benzimidazole is one of the privileged nitrogen-containing scaffolds known for its versatile diversified role in insecticides, pesticides, dyes, pigments and pharmaceuticals. Due to its electron-rich environment, structural features and binding potency of various therapeutic targets, benzimidazole derivatives exhibit a broad spectrum of biological activity that majorly includes antimicrobial, antifungal, analgesics, anti-diabetic and anticancer agents. Several benzimidazole scaffolds bearing drugs are clinically approved; they are used for various indications. For example, Bilastine, Lerisetron, Maribavir and Nocodazole are the most widely used benzimidazole-based marketed drugs available as an antihistamine, antiviral and antimitotic agent, respectively. Another example is the recently approved anticancer drug Binimetinib and Selumetinib, which are indicated for BRAF mutated melanoma and plexiform neurofibromas. Not only this, many benzimidazole-based anticancer drugs are in late phases of clinical development. Due to the vast therapeutic potential of benzimidazole scaffold in cancer research, medicinal chemists have gained a lot of attraction to explore it more and develop novel, highly effective and target-specific benzimidazole-based potential anticancer drugs.

scholarly journals Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink

2016 ◽  
Vol 113 (6) ◽  
pp. 1630-1635 ◽  
Author(s):  
Maxwell Z. Wilson ◽  
Rurun Wang ◽  
Zemer Gitai ◽  
Mohammad R. Seyedsayamdost
Keyword(s):  
Broad Spectrum ◽  
Marine Bacteria ◽  
Anticancer Agents ◽  
Mode Of Action ◽  
Resistance Mechanism ◽  
Acid Resistance ◽  
Structural Features ◽  
Anticancer Activities ◽  
Tropodithietic Acid ◽  
Biochemical Analyses

While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal–bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA’s cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.

scholarly journals Chirality in Anticancer Agents

2021 ◽  
Author(s):  
Jindra Valentová ◽  
Lucia Lintnerová
Keyword(s):  
Biological Activity ◽  
Antitumor Activity ◽  
Nucleic Acids ◽  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Biological Molecules ◽  
Therapeutic Activity ◽  
Specific Recognition

Many drugs are chiral and their therapeutic activity depends on specific recognition of chiral biomolecules. The biological activity of enantiomers can also differ drastically in terms of toxicity and pharmacokinetics. Chiral natural biological molecules, such as nucleic acids, enzymes are targeted molecules for the development of anticancer drugs. The interest in chiral agents is logically a result of the different interaction with biomolecules leading in the end consequence to improve anticancer activity and maybe to less undesirable effects. This review outlines the effects of chirality on the efficiency of anticancer metal-based agents and potential organic drugs. A variety of up-to-date examples of structurally diverse chiral agents exhibiting different mechanisms in their antitumor activity is presented.

A Panoramic Review of Benzimidazole Derivatives and Their Potential Biological Activity

2022 ◽  
Vol 22 ◽  
Author(s):  
Hiram Hernández-López ◽  
Christian Jairo Tejada-Rodríguez ◽  
Socorro Leyva-Ramos
Keyword(s):  
Biological Activity ◽  
Hydrophobic Interactions ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Benzimidazole Derivatives ◽  
Drug Candidate ◽  
Hydrogen Bond Donor ◽  
Wide Range ◽  
Donor Acceptor ◽  
Potent Drug

Abstract: The therapeutic potential of the benzimidazole nucleus dates back to 1944, being and important heterocycle system due to its presence in a wide range of bioactive compounds such as antiviral, anticancer, antibacterial, and so on, where optimization of substituents in this class of pharmacophore has resulted in many drugs. Its extensive biological activity is due to its physicochemical properties like hydrogen bond donor-acceptor capability,  stacking interactions, coordination bonds with metals as ligands and hydrophobic interactions; properties that allow them to easily bind with a series of biomolecules, including enzymes and nucleic acids, causing a growing interest in these types of molecules. This review aims to present an overview to leading benzimidazole derivatives, as well as to show the importance of the nature and type of substituents at the N1, C2, and C5(6) positions, when they are biologically evaluated, which can lead to obtaining potent drug candidate with significant range of biological activities.

scholarly journals Development of a Streptomyces venezuelae-Based Combinatorial Biosynthetic System for the Production of Glycosylated Derivatives of Doxorubicin and Its Biosynthetic Intermediates

2011 ◽  
Vol 77 (14) ◽  
pp. 4912-4923 ◽  
Author(s):  
Ah Reum Han ◽  
Je Won Park ◽  
Mi Kyeong Lee ◽  
Yeon Hee Ban ◽  
Young Ji Yoo ◽  
...  
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Important Determinant ◽  
Biosynthetic Enzymes ◽  
Streptomyces Venezuelae ◽  
Content Type ◽  
Biological Tool ◽  
Derivatives Of

ABSTRACTDoxorubicin, one of the most widely used anticancer drugs, is composed of a tetracyclic polyketide aglycone andl-daunosamine as a deoxysugar moiety, which acts as an important determinant of its biological activity. This is exemplified by the fewer side effects of semisynthetic epirubicin (4′-epi-doxorubicin). An efficient combinatorial biosynthetic system that can convert the exogenous aglycone ε-rhodomycinone into diverse glycosylated derivatives of doxorubicin or its biosynthetic intermediates, rhodomycin D and daunorubicin, was developed through the use ofStreptomyces venezuelaemutants carrying plasmids that direct the biosynthesis of different nucleotide deoxysugars and their transfer onto aglycone, as well as the postglycosylation modifications. This system improved epirubicin production from ε-rhodomycinone by selecting a substrate flexible glycosyltransferase, AknS, which was able to transfer the unnatural sugar donors and a TDP-4-ketohexose reductase, AvrE, which efficiently supported the biosynthesis of TDP-4-epi-l-daunosamine. Furthermore, a range of doxorubicin analogs containing diverse deoxysugar moieties, seven of which are novel rhodomycin D derivatives, were generated. This provides new insights into the functions of deoxysugar biosynthetic enzymes and demonstrates the potential of theS. venezuelae-based combinatorial biosynthetic system as a simple biological tool for modifying structurally complex sugar moieties attached to anthracyclines as an alternative to chemical syntheses for improving anticancer agents.

scholarly journals Synthesis and Characterization of Benzimidazole Derivatives for Antimicrobial Property

2021 ◽  
Vol 6 (8) ◽  
pp. 134-143
Author(s):  
Choudhary Kapil ◽  
Bhavsar Rupali ◽  
Chaturvedi Prerna
Keyword(s):  
Ethyl Acetate ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Antimicrobial Property ◽  
Glass Plate ◽  
Anthelmintic Activity ◽  
Structural Features ◽  
High Yield ◽  
Benzimidazole Derivatives ◽  
Standard Drug

Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-microbial, antitumor and anthelmintic activity. Benzimidazole rings are the most important nitrogen-containing heterocycles, which are widely explored and utilized by the pharmaceutical industry for drug discovery. Due to their special structural features and electron-rich environment, Benzimidazole containing drugs bind to a variety of therapeutic targets, thereby exhibiting a broad spectrum of bioactivities. Numerous benzimidazole based drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potential. The main objective of present work was to study the anti-microbial activity of the Benzimidazole drivatives. A series of benzimidzole derivatives have been synthesized and identified. The compounds were synthesized by using ethyl acetate and benzene as starting material. The series of 1, 2-disubstituted benzimidazoles containing pyrimidine and other functional groups was prepared which provides advantages such as, easy workup and high yield. All reagents used for synthesis were of synthetic grade. Purification of all compounds was done by thin layer chromatography using silica gel G as absorbent on glass plate using acetate: benzene (6:4 v/v %), Toluene: Acetone (8:2 v/v %) and Ethyl Acetate: n- Hexane (6:4 v/v %) as mobile phase. Compounds were detected by using iodine vapor as detecting agent. All compounds show single spot. All the newly synthesized compounds were characterized by IR spectral study. The compounds were investigated for their antimicrobial activity against clinical standard drug Ciprofloxacin. The anti-microbial study of the synthesized derivative was done Broad panels of bacterial and fungal strains were used for testing the antimicrobial properties of the synthesized molecules III1-13. The compounds III1 (m-NO2), III2 (p-NO2), III3 (m-Cl), III4 (3-F-4-Cl) and III9 (p-OCH3) showed excellent activity (62.5 μg/ml), even better than ciprofloxacin.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics

2020 ◽  
Vol 17 (7) ◽  
pp. 558-576 ◽  
Author(s):  
Biman Kumar Panigrahi ◽  
Amit Kumar Nayak
Keyword(s):  
Carbon Nanotubes ◽  
Drug Delivery ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Cancer Therapeutics ◽  
Physicochemical Characteristics ◽  
Structural Features ◽  
Noncovalent Interaction ◽  
Bioactive Molecules ◽  
Anticancer Drug Delivery

Background: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. Objective: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. Methods: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via the loading of various anticancer agents. Results: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. Conclusion: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

scholarly journals Biological Activity of Phenolic Compounds in Extra Virgin Olive Oils through Their Phenolic Profile and Their Combination with Anticancer Drugs Observed in Human Cervical Carcinoma and Colon Adenocarcinoma Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 453 ◽  
Author(s):  
Jelena Torić ◽  
Anamaria Brozovic ◽  
Mirela Baus Lončar ◽  
Cvijeta Jakobušić Brala ◽  
Ana Karković Marković ◽  
...  
Keyword(s):  
Biological Activity ◽  
Olive Oil ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Biological Effect ◽  
Dependent Manner ◽  
Phenolic Profile ◽  
Virgin Olive Oils ◽  
Olive Oils

The roles of phenolics from olive oils as effective anticancer agents have been documented in various in vitro studies of different cancer cells lines, but the relationship between the phenolic profile of olive oil and its biological activity needs more elucidation. In this study, we analysed phenolic profiles of extra virgin olive oils (EVOOs) from different autochthonous cultivars from Croatia (Oblica, Bjelica, Buža, Žižolera) and investigated the biological effect of EVOO phenolic extracts (EVOO-PEs) on human cervical (HeLa) and human colon (SW48) cancer cell lines alone and in combination with cisplatin (cDDP), carboplatin (CBP), 5-fluorouracil (5-FU) and irinotecan. The quantitative evaluation of olive oil polyphenols was performed by HPLC-DAD and spectrophotometric analysis. The biological effect of EVOO-PEs alone and in combination with anticancer drugs was measured by MTT assay. Analysed EVOO-PEs differ in phenolic profile and inhibited HeLa and SW48 cells in a dose-dependent manner. Further, it is shown that EVOO-PEs (Oblica-Sea, Buža and Žižolera), in combination with anticancer drugs, increase the metabolic activity of HeLa and SW48 cells and have a protective role. These data imply careful consummation of olive oil during chemotherapy of cancer patients.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai
Keyword(s):  
Biological Activity ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Research Field ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
The Family ◽  
Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

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