New chalcone derivatives having pyrazole and sulfonamide pharmacophores as carbonic anhydrase inhibitors

Background: Sulfonamide, pyrazole and chalcone pharmacophores are an important compounds in medicinal chemistry. They have wide range of biological activities including carbonic anhydrase (CA) inhibitory activities. Introduction: Carbonic anhydrase I and II inhibitors are used for the treatment of some disease such as retinal and cerebral edema (CAI), edema, epilepsy, and glaucoma (CA II). The available drugs in market have some limitations or side effect problems. So, there is a need to develop new drug candidate compound/s to overcome the problems at issue. In this study, a series of compounds MS4-MS10, (E)-4-(4-(3-aryl)-3-oxoprop-1-en-1-yl)-3-phenyl-1H-pyrazol-1-yl) benzenesulfonamides, were designed to discover new carbonic anhydrase inhibitors using hibryd approach. Methods: The compounds MS4-MS10 were synthesized as shown in Scheme 1 and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Carbonic anhydrase (CAs, E.C.4.2.1.1) inhibitory effects of MS4-MS10 were tested on the hCA I and II isoenzymes by previously reported procedures. Results and Discussons: Carbonic anhydrase inhibitors results of the MS4-MS10 were presented in Table 1 as IC50 values (nM). They were inhibition range of 27.8-87.3 towards hCA I and 24.4-54.8 towards hCA II while reference drug AAZ IC50 values were 384.2 (hCA I) and 36.9 (hCA II). MS7 and MS9 had 13.8 (hCA I) and 1.5 (hCA II) times more potent CA inhibition than reference compound AAZ, respectively. Conclusion: MS7 (Ar: 2,4,5-trimethoxy phenyl) towards hCA I and MS9 (Ar: 3,4-dimethoxy phenyl) towards hCA II were the lead compounds of our series with the lowest IC50 value and can be considered for further studies.

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Synthesis, Antioxidant and Antiurease Activities of Some New 5,6- dichloro-2-(4-fluorobenzyl)-1H-benzimidazole Derivatives Containing Furan, Oxadiazole, Triazole and Thiadiazole Moieties

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180827124956 ◽

2019 ◽

Vol 16 (8) ◽

pp. 939-947

Author(s):

Hakan Bektas ◽

Canan Albay ◽

Emre Menteşe ◽

Bahar Bilgin Sokmen ◽

Zafer Kurt ◽

...

Keyword(s):

Biological Activities ◽

Benzimidazole Derivatives ◽

Wide Range ◽

Ic50 Values ◽

Urease Inhibitory

Background:Benzimidazoles and its derivatives have been attracting interest for many years because of their biological activities. Benzimidazoles containing different heterocyclic moieties have wide range of biological activities such as antimicrobial, antioxidant, anticancer, antiviral, etc.Methods:In this study, some benzimidazole derivatives containing furan, oxadiazole, triazole and thiadiazole moieties have been synthesized and then evaluated for their antioxidant and antiurease activities.Results:The results showed that all the tested benzimidazoles indicated remarkable urease inhibitory potentials with IC50 values ranging between 0.303±0.03 to 0.591±0.08 µM.Conclusion:In conclusion, synthesized benzimidazole derivatives showed good antioxidant and antiurease activities. Heterocyclic groups on benzimidazole nucleus enhance the activities.

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Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527320666210602152308 ◽

2021 ◽

Vol 20 ◽

Author(s):

Subham Das ◽

Saleem Akbar ◽

Bahar Ahmed ◽

Rikeshwar Prasad Dewangan ◽

Mohammad Kashif Iqubal ◽

...

Keyword(s):

Biological Activities ◽

Neuroprotective Agents ◽

Wide Range ◽

Recent Developments ◽

Ic50 Values ◽

Structural Activity Relationship ◽

Pharmaceutical Industries ◽

Neurological Conditions ◽

Nitrogen Containing Compounds

: As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact on chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is to discover novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

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Biological Activity of Bicyclic and Tricyclic Diterpenoids from Salvia Species of Immediate Pharmacological and Pharmaceutical Interest

Natural Product Communications ◽

10.1177/1934578x1100600839 ◽

2011 ◽

Vol 6 (8) ◽

pp. 1934578X1100600 ◽

Cited By ~ 3

Author(s):

Maria Carmela Bonito ◽

Carla Cicala ◽

Maria Carla Marcotullio ◽

Francesco Maione ◽

Nicola Mascolo

Keyword(s):

Biological Activities ◽

Folk Medicine ◽

Plant Defence ◽

Experimental Studies ◽

Scientific Basis ◽

Chemical Structures ◽

Wide Range ◽

Real Value ◽

Antimicrobic Activity ◽

Cyclic Compounds

Diterpenoids are a class of compounds that derive from the condensation of four isoprene units that leads to a wide variety of complex chemical structures, including acyclic bi-, tri-and tetra-cyclic compounds; in Salvia species, only bi-, tri-and tetra-cyclic compounds have been found. This review covers a wide range of biological activities and mode of action of diterpenoids isolated from Salvia species that might raise some pharmacological and pharmaceutical interest. We have produced a synoptic table where the biological activities of the main active principles are summarized. Our analysis emphasizes that diterpenoids from Salvia species continue to be a plant defence system since their antimicrobic activity. Experimental studies show that most of diterpenoids considered have cytotoxic and / or antiproliferative activity. Some of them have also cardiovascular and central effects. In a less extended manner, diterpenoids from Salvia species show gastrointestinal, urinary, antinflammatory, antidiabetic, ipolipidemic and antiaggregating effects. In the last decade, several clinical trials have been developed in order to investigate the real value of Salvia extracts treatment; results obtained are promising and confer scientific basis in the use of medicinal plants from folk medicine.

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Sesquiterpenes-Rich Essential Oil from Above Ground Parts of Pulicaria somalensis Exhibited Antioxidant Activity and Allelopathic Effect on Weeds

Agronomy ◽

10.3390/agronomy10030399 ◽

2020 ◽

Vol 10 (3) ◽

pp. 399 ◽

Cited By ~ 6

Author(s):

Abdulaziz Assaeed ◽

Abdelsamed Elshamy ◽

Abd El-Nasser El Gendy ◽

Basharat Dar ◽

Saud Al-Rowaily ◽

...

Keyword(s):

Essential Oil ◽

Biological Activities ◽

Allelopathic Effect ◽

Bidens Pilosa ◽

Specific Chemical ◽

Genetic Characteristics ◽

Dactyloctenium Aegyptium ◽

Ic50 Value ◽

Ic50 Values ◽

Main Components

Pulicaria genus (fleabane) is characterized by its fragrant odor due to the presence of essential oil (EO). According to the literature reviews, the EO of Pulicaria somalensis O.Hoffm. (Shie) is still unexplored. For the first time, 71 compounds were characterized in EO derived from above-ground parts of P. somalensis collected from Saudi Arabia. Sesquiterpenes represented the main components (91.8%), along with minor amounts of mono-, diterpenes, and hydrocarbons. Juniper camphor (24.7%), α-sinensal (7.7%), 6-epi-shyobunol (6.6%), α-zingiberene (5.8%), α-bisabolol (5.3%), and T-muurolol (4.7%) were characterized as main constituents. The correlation analysis between different Pulicaria species showed that P. somalensis has a specific chemical pattern of the EO, thereby no correlation was observed with other reported Pulicaria species. The EO showed significant allelopathic activity against the weeds of Dactyloctenium aegyptium (L.) Willd. (crowfoot grass) and Bidens pilosa L. (hairy beggarticks). The IC50 value on the germination of D. aegyptium was double that of B. pilosa. The IC50 values on the root growth of B. pilosa and D. aegyptium were 0.6 mg mL−1 each, while the shoot growths were 1.0 and 0.7 mg mL−1, respectively. This variation in the activity could be attributed to the genetic characteristics of the weeds. Moreover, the EO exhibited significant antioxidant effects compared to ascorbic acid. Further studies are necessary to verify if these biological activities of the EO could be attributable to its major compounds.

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A Review of Terpenes from Marine-Derived Fungi: 2015–2019

Marine Drugs ◽

10.3390/md18060321 ◽

2020 ◽

Vol 18 (6) ◽

pp. 321 ◽

Cited By ~ 4

Author(s):

Minghua Jiang ◽

Zhenger Wu ◽

Heng Guo ◽

Lan Liu ◽

Senhua Chen

Keyword(s):

Enzyme Inhibitor ◽

Biological Activities ◽

Chemical Diversity ◽

Active Metabolites ◽

Marine Animals ◽

Research Papers ◽

Lead Compounds ◽

Chemical Structures ◽

The Past ◽

Pharmacologically Active

Marine-derived fungi are a significant source of pharmacologically active metabolites with interesting structural properties, especially terpenoids with biological and chemical diversity. In the past five years, there has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered. In this updated review, we examine the chemical structures and bioactive properties of new terpenes from marine-derived fungi, and the biodiversity of these fungi from 2015 to 2019. A total of 140 research papers describing 471 new terpenoids of six groups (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and meroterpenes) from 133 marine fungal strains belonging to 34 genera were included. Among them, sesquiterpenes, meroterpenes, and diterpenes comprise the largest proportions of terpenes, and the fungi genera of Penicillium, Aspergillus, and Trichoderma are the dominant producers of terpenoids. The majority of the marine-derived fungi are isolated from live marine matter: marine animals and aquatic plants (including mangrove plants and algae). Moreover, many terpenoids display various bioactivities, including cytotoxicity, antibacterial activity, lethal toxicity, anti-inflammatory activity, enzyme inhibitor activity, etc. In our opinion, the chemical diversity and biological activities of these novel terpenoids will provide medical and chemical researchers with a plenty variety of promising lead compounds for the development of marine drugs.

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Antileishmanial activity of some Brazilian plants, with particular reference to Casearia sylvestris

Anais da Academia Brasileira de Ciências ◽

10.1590/0001-3765201520140288 ◽

2015 ◽

Vol 87 (2) ◽

pp. 733-742 ◽

Cited By ~ 10

Author(s):

Luciana M.R. Antinarelli ◽

Nícolas C. Pinto ◽

Elita Scio ◽

Elaine S. Coimbra

Keyword(s):

Leishmania Species ◽

Herbal Remedies ◽

Poor People ◽

Reference Drug ◽

Tropical Plants ◽

Ic50 Value ◽

Collateral Effects ◽

Ic50 Values ◽

Casearia Sylvestris ◽

Expressive Activity

Leishmaniasis is a complex of diseases caused by Leishmania protozoa which treatment is restricted to a limited number of drugs that exhibit high toxicity, collateral effects and are often costly. There are a variety of tropical plants distributed in Brazil, and for many poor people the therapy for several diseases is based mainly on the use of traditional herbal remedies. In this work, the cytotoxic activity of 17 plant methanol extracts was evaluated on several Leishmania species and murine macrophages. Among them, the extract of Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea tubulosa and Plectranthus neochilus showed a promissing leishmanicidal activity, exhibiting IC50 values below of 20 µg/mL against at least one species of Leishmania. Casearia sylvestris showed the most expressive activity against all promastigote forms of Leishmania species (IC50 values of 5.4 µg/mL, 5.0 µg/mL, 8.5 µg/mL and 7.7 µg/mL for L. amazonensis, L. braziliensis, L. chagasi and L. major, respectively), being more effective than the reference drug miltefosine. In spite of the cytotoxic effect on macrophages (CC50 value of 5.2 µg/mL), C. sylvestris exhibited a strong inhibition against intracellular amastigotes of L. braziliensis (IC50 value of 1.3 µg/mL). Further studies, including bio-guided fractionation will be conducted to identify the active compounds.

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Development of Nimesulide Analogues as Dual Tubulin and HSP27 Inhibitor for Treating Female Cancers

10.20944/preprints202009.0523.v1 ◽

2020 ◽

Author(s):

Laila Jarragh Alhadad ◽

Fars Alanazi ◽

Gamaleldin Harisa

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cell Lines ◽

Biological Activities ◽

Critical Role ◽

Biological Evaluation ◽

Crystallographic Analysis ◽

Skbr3 Cell ◽

Chemical Structures ◽

Ic50 Values

Tubulin and heat shock protein 27 (HSP27) are up-regulated in cancer cells, and play a critical role in cell division, and proliferation. Therefore, they are targets for discovery of anticancer therapy. The objective of this study is to design, characterize, and biologically evaluate the nimesulide analogues to combat female cancer such as ovarian cancer, and breast cancer. Herein, the nimesulide analogues are designed to target both tubulin and HSP27 functions. Ovarian cancer (SKOV3) and breast cancer (SKBR3) cell lines were used as surrogate models to test the nimesulide analogs biological activities using MTT assay. In the present study, four nimesulide analogues were designed, synthesized and the chemical structures were with the biological evaluation were studied. The synthesized agents were characterized by 1H-NMR, 13C-NMR, the molecular weight was confirmed using GC-MS technique, and melting point. Besides, the agent L4 structure was confirmed using X-ray crystallographic analysis. The present data revealed that nimesulide analogs have potent anticancer activity against SKOV3and SKBR3 cell lines. The IC50 values for both SKOV3 and SKBR3 cell lines treated with the agents showed a potent cell growth inhibition range of 0.23-2.02 µM and 0.50-3.73 µM respectively. In conclusion, the designed nimesulide analogues can target both tubulins, and HSP27 concurrently, and they are promising agents as future chemotherapy female cancers.

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Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity

Molecules ◽

10.3390/molecules25225226 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5226

Author(s):

Yi-Fei Gu ◽

Yue Zhang ◽

Feng-li Yue ◽

Shao-tong Li ◽

Zhuo-qi Zhang ◽

...

Keyword(s):

Biological Activities ◽

Collagen Type I ◽

Type I ◽

The Novel ◽

Pyrimidine Derivatives ◽

Wide Range ◽

Ic50 Values ◽

Privileged Structures ◽

Pyrimidine Moiety

A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC50 values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.

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A Panoramic Review of Benzimidazole Derivatives and Their Potential Biological Activity

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557522666220104150051 ◽

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.

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New Hybrid Compounds Combining Fragments of Usnic Acid and Monoterpenoids for Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibition

Biomolecules ◽

10.3390/biom11070973 ◽

2021 ◽

Vol 11 (7) ◽

pp. 973

Author(s):

Nadezhda S. Dyrkheeva ◽

Aleksandr S. Filimonov ◽

Olga A. Luzina ◽

Alexandra L. Zakharenko ◽

Ekaterina S. Ilina ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

Biological Activities ◽

Usnic Acid ◽

Topoisomerase 1 ◽

Binding Domains ◽

Promising Therapeutic Target ◽

Wide Range ◽

Ic50 Values ◽

Low Cytotoxicity

Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabilized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cytotoxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protective” effect from topotecan on non-cancerous cells requires further investigation.

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