scholarly journals 4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 9 ◽  
Author(s):  
Martin Krátký ◽  
Klára Konečná ◽  
Jiří Janoušek ◽  
Michaela Brablíková ◽  
Ondřej Janďourek ◽  
...  
Keyword(s):  
Schiff Bases ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Antimycobacterial Activity ◽  
Cytotoxic Agents ◽  
Aminobenzoic Acid ◽  
Human Pathogens ◽  
Essential Nutrient ◽  
One Step ◽  
Imine Bond

4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC50 ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.

Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues

2018 ◽  
Vol 18 (1) ◽  
pp. 121-138 ◽  
Author(s):  
Mohamed Jawed Ahsan ◽  
Arun Choupra ◽  
Rakesh Kumar Sharma ◽  
Surender Singh Jadav ◽  
Pannala Padmaja ◽  
...  
Keyword(s):  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Cytotoxic Agents ◽  
Tubulin Polymerization ◽  
Sodium Bisulphite ◽  
Tubulin Inhibitor ◽  
Tubulin Inhibitors ◽  
Drug Concentrations

Background: 1,3,4-Oxadiazole heterocycles possess a broad spectrum of biological activities. They were reported as potent cytotoxic agents and tubulin inhibitors; hence it is of great interest to explore new oxadiazoles as cytotoxic agents targeting tubulin polymerization. Objective: Two new series of oxadiazoles (5a-h and 12a-h) were synthesized, structurally related to the heterocyclic linked aryl core of IMC-038525, NSC 776715, and NSC 776716, with further modification by incorporating methylene linker. Method: The 2,5-disubstituted-1,3,4-oxadiazoles (5a-h and 12a-h) were synthesized by refluxing an equimolar mixture of the intermediates [(4) and (8a-d)] and aromatic aldehydes in water-ethanol system using sodium bisulphite catalyst. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI US) Protocol, while the tubulin polymerization assay kits from Cytoskeleton ™(bk011p) was used to perform an in vitro tubulin polymerization assay. Results: 2-(5-{[(4-Chlorophenyl)amino]methyl}-1,3,4-oxadiazol-2-yl)phenol (5f) and 2-[(2,4-dichlorophenoxy) methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole (12c) showed maximum cytotoxicity with the mean percent growth inhibitions (GIs) of 71.56 and 72.68 respectively at 10 µM drug concentrations. Both the compounds (5f and 12c) showed superior cytotoxicity than clinically prevalent anticancer drugs, Imatinib and Gefitinib in one dose assay. The compound 12c showed promising results in five dose assay, with GI50 values varies between 1.61 and >100 µM. Furthermore, the compounds, 5f and 12c also inhibited the polymerization of tubulin with, an IC50 of 2.8 and 2.2 µM, respectively. Conclusion: The oxadiazoles reported herein are tubulin inhibitors and cytotoxic agents. These findings will be helpful in future drug design of more potent tubulin inhibitor cytotoxic agents.

scholarly journals Synthesis, Identification and Biological Activity of New Heterocyclic Compounds from Reaction of New Schiff-Bases with Phathalic Anhydride

2020 ◽  
Vol 8 (1) ◽  
pp. 12-18
Author(s):  
Alya A. Dawood ◽  
Shireen R. Mmohammed ◽  
Mohammed Mahmoud
Keyword(s):  
Acetic Acid ◽  
Schiff Bases ◽  
Heterocyclic Compounds ◽  
Mass Spectra ◽  
Glacial Acetic Acid ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Aromatic Aldehydes ◽  
Heterocyclic Ring ◽  
Second Step

Series of new Schiff bases and their derivatives (Oxazepine) have been synthesized during two steps. The first step synthesis of imines derivatives (1-10) by the condensation reaction of 1, 7-diaminohepatane and 1,8-diaminooctane with different substituted aromatic aldehydes by using glacial acetic acid as catalyst. The second step includes reaction of the prepared Schiff bases derivatives with phathalic anhydride in dry benzene to obtain   seven-membered heterocyclic ring derivatives (11-15).  The biological activities of some prepared compounds were also studied against different kinds of bacteria. The new derivatives were confirmed by suing a range of experimental techniques including 1HNMR, 13C NMR, IR and Mass spectra.

scholarly journals Synthesis and Evaluation of Anticonvulsant Activity of Some Quinazoline Analogues

2021 ◽  
pp. 147-154
Author(s):  
Surajmal G. Malpani ◽  
Pradeepkumar Mohanty ◽  
Janki Prasad Rai
Keyword(s):  
Aromatic Ring ◽  
Schiff Bases ◽  
Anticonvulsant Activity ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Pharmacological Agent ◽  
Control Group ◽  
Synthetic Route ◽  
Delayed Onset ◽  
Electron Withdrawing Group

Aim: A new series of Quinazoline 4(3H)-one derivative were prepared by reacting quinazoline 4(3H)-one hydrazide with substituted aromatic aldehydes. Quinazoline is used as a potent pharmacological agent with various biological activities such as antimicrobial, antiviral, antitumor, convulsion, anxiety, anti-inflammatory, and analgesic. In this background, we have synthesized a series of Quinazoline 4(3H)-one derivatives (4a-4f) and screened for their anticonvulsant activity.  Methods: In this work, Schiff bases were prepared by treating quinazoline 4(3H)-one hydrazide with aromatic aldehydes. Six compounds (4a-4f) were screened for anticonvulsant activity by Isoniazid (INH) and Pentylenetetrazole (PTZ) induced convulsions in mice. Results: All the compounds were given satisfactory reaction yields that representing the efficiency of the employed synthetic route. In INH induced convulsion model, delayed the onset of convulsion significantly 4a, 4b, 4d, 4e, 4f when compared to an induction control group. Whereas delayed onset of convulsion was non-significant for 4c. In PTZ induced convulsion model, delayed the onset of convulsion significantly 4a, 4d, 4e, 4f when compared to induction control group. Whereas delayed onset of convulsion was non-significant for 4b and 4c. Conclusion: This indicates the anticonvulsant activity to these derivatives which might be due to potentiating GABA activity in the CNS. This anticonvulsant activity was due to presence of electron-donating group like OH, NH2, OCH3 and electron-withdrawing group like CF3 at 2nd and 4th position of aromatic ring attached to hydrazide.

Activities of Thiazolidine-4-one and Azetidine-2-one Derivatives- A Review

2021 ◽  
pp. 4513-4516
Author(s):  
Ramachandran S. ◽  
Binoy Varghese Cheriyan ◽  
M. Vijey Aanandhi
Keyword(s):  
Yellow Fever Virus ◽  
Biological Activities ◽  
Bond Formation ◽  
Antidepressant Activity ◽  
Aromatic Aldehydes ◽  
Antimycobacterial Activity ◽  
Primary Amines ◽  
Antihypertensive Activity ◽  
Anti Inflammatory ◽  
Almost All

Thiazolidine-4-ones containing thiazole moiety have been synthesized by condensing 6-amino Coumarin, Isatin and Primary amines, and aromatic aldehydes. Azetidine derivates were synthesized followed by cyclizations by C-N bond formation and by the C-C bond formation, the amine-catalyzed cycloaddition of allenoates and imines, photocycloadditions of imines and alkenes, ring contraction and expansion rearrangements, and reduction of azetidine-2-ones (β-lactams). Thiazolidine-4-ones has been considered as a magic moiety because it posses almost all types of biological activities such as Antifungal, Antitubercular, Antimicrobial, Antioxidant, Antibacterial, Cytotoxic, Anti-inflammatory, Analgesic, Anti YFV (yellow fever virus) activities. Azetidine-2-one derivatives were reported to possess antibacterial, antifungal and antidepressant activity, anticonvulsant activity, anti-inflammatory activity and cardiovascular activities, antimycobacterial activity, antihypertensive activity. This article is a review of various biological activities of thiazolidine-4-ones and Azetidine-2-ones derivatives.

Bioactive Secondary Metabolites from Endophytic Fungi

2020 ◽  
Vol 27 (11) ◽  
pp. 1836-1854 ◽  
Author(s):  
Elena Ancheeva ◽  
Georgios Daletos ◽  
Peter Proksch
Keyword(s):  
Secondary Metabolites ◽  
Endophytic Fungi ◽  
Host Plants ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Special Focus ◽  
Plant Metabolites ◽  
Direct Production ◽  
Bioactive Secondary Metabolites ◽  
Fungal Genes

Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants. Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.

Synthesis, Characterization, Anti-proliferative Evaluation, and DNA Flow Cytometry Analysis of Some 2-Thiohydantoin Derivatives

2020 ◽  
Vol 20 (18) ◽  
pp. 1929-1941
Author(s):  
Heba A. Elhady ◽  
Hossa F. Al-Shareef
Keyword(s):  
Anticancer Activity ◽  
Schiff Bases ◽  
Anticancer Agents ◽  
Proliferative Activity ◽  
Cancer Cell Line ◽  
Aromatic Aldehydes ◽  
Pharmaceutical Chemistry ◽  
Dna Flow Cytometry ◽  
Quinazoline Derivative ◽  
Reference Drug

Background and Objective: Due to the well-documented anti-proliferative activity of 2-thiohydantoin incorporated with pyrazole, oxadiazole, quinazoline, urea, β-naphthyl carbamate and Schiff bases, they are noteworthy in pharmaceutical chemistry. Methods: An efficient approach for the synthesis of a novel series of 2-thiohydantoin derivatives incorporated with pyrazole and oxadiazole has proceeded via the reaction of the acyl hydrazide with chalcones and/or triethyl orthoformate. Schiff bases were synthesized by the reaction of the acyl hydrazide with different aromatic aldehydes. Moreover, Curtius rearrangement was applied to the acyl azide to obtain the urea derivative, quinazoline derivative, and carbamate derivative. Results: The synthesized compounds structures were discussed and confirmed depending on their spectral data. The anticancer activity of these heterocyclic compounds was evaluated against the breast cancer cell line (MCF-7), where they showed variable activity. Compound 5d found to have a superior anticancer activity, where it has (IC50 = 2.07 ± 0.13 μg/mL) in comparison with the reference drug doxorubicin that has (IC50 = 2.79 ± 0.07 μg / mL). Then compound 5d subjected to further studies such as cell cycle analysis and apoptosis. Apoptosis was confirmed by the upregulation of Bax, downregulation of Bcl-2, and the increase of the caspase 3/7percentage. Conclusion: Insertion of pyrazole, oxadiazole and, quinazoline moieties with 2-thiohydantoin moiety led to the enhancement of its anti-proliferative activity. Hence they can be used as anticancer agents.

Evaluation of Pyrano[3,2 C] Quinoline Analogues as Anticancer Agents

2019 ◽  
Vol 19 (10) ◽  
pp. 1285-1292 ◽  
Author(s):  
Kuldip D. Upadhyay ◽  
Anamik K. Shah
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Tumor Growth Inhibition ◽  
Mice Model ◽  
One Pot ◽  
Aryl Ring ◽  
Hct 116

Background: Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. Objective: The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its cytotoxicity. Methods: A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model. Results: The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in HCT-116 tumor mice model. Conclusion: The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3- chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold and outcome with compound 4c as the most potent candidate of the series.

DFT Study and Synthesis of Novel Bioactive Bispyrazole Using Mg/AlLDH as a Solid Base Catalyst

2020 ◽  
Vol 14 ◽  
Author(s):  
Soufiane Akhramez ◽  
Youness Achour ◽  
Mustapha Diba ◽  
Lahoucine Bahsis ◽  
Hajiba Ouchetto ◽  
...  
Keyword(s):  
Dft Calculations ◽  
Experimental Finding ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Aromatic Aldehydes ◽  
Mechanistic Study ◽  
Knoevenagel Reaction ◽  
Solid Base ◽  
Reaction Conditions ◽  
Aryl Aldehyde

Background: In this study, an efficient synthesis of novel bispyrazole heterocyclic molecules by condensation of substituted aromatic aldehydes with 1,3-diketo-N-phenylpyrazole by using Mg/Al-LDH as heterogeneous catalyst is reported. The attractive features of this protocol are as follows: mild reaction conditions, good yields and easiness of the catalyst separation from the reaction mixture. Further, a mechanistic study has been performed by using DFT calculations to explain the observed selectivity of the condensation reaction between aryl aldehyde and 1,3-diketo-N-phenylpyrazole via Knoevenagel reaction. The local electrophilicity/ nucleophilicity that allows explaining correctly the experimental finding. Methods: The bispyrazole derivatives 3a-m were prepared by condensation reaction of substituted aromatic aldehydes with 1,3-diketo-Nphenylpyrazole by using Mg/Al-LDH as heterogeneous catalyst under THF solvent at the refluxing temperature. Objective: To synthesize a novel bispyrazole heterocyclic molecule may be have important biological activities and thus can be good candidates for pharmaceutical applications. Results: This protocol describes the Synthesis of Bioactive Compounds under mild reaction conditions, good yields and easiness of the catalyst separation from the reaction mixture. Further, a mechanistic study has been performed by using DFT calculations to explain the observed selectivity of the condensation reaction between aryl aldehyde and 1,3-diketo-N-phenylpyrazole via Knoevenagel reaction. The local electrophilicity/ nucleophilicity that allows explaining correctly the experimental finding. Conclusion: In summary, the pharmacologically interesting bis-pyrazole derivatives have been synthesized through Mg/Al-LDH as a solid base catalyst, in THF as solvent. Thus, the synthesized bioactive compounds containing the pyrazole ring may be have important biological activities and thus can be good candidates for pharmaceutical applications. Therefore, the catalyst Mg/Al-LDH showed high catalytic activity. Besides, a series of bispyrazole molecules were synthesized with a good yield and easy separation of the catalyst by simple filtration. Moreover, DFT calculations and reactivity indexes are used to explain the selectivity of the condensation reaction between aryl benzaldehyde and 1,3-diketo-Nphenylpyrazole via Knoevenagel reaction, and the results are in good agreement with the experimental finding.

scholarly journals Pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amines as Potential Cytotoxic Agents against Human Neuroblastoma

2021 ◽  
Vol 14 (8) ◽  
pp. 750
Author(s):  
Zahira Tber ◽  
Mohammed Loubidi ◽  
Jabrane Jouha ◽  
Ismail Hdoufane ◽  
Mümin Alper Erdogan ◽  
...  
Keyword(s):  
Cell Line ◽  
Drug Exposure ◽  
Caspase 3 ◽  
Biological Activities ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Parp 1

We report herein the evaluation of various pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amines as potential cytotoxic agents. These molecules were obtained by developing the multicomponent Groebke–Blackburn–Bienaymé reaction to yield various pyrido[2′,1′:2,3]imidazo[4,5-c]quinolines which are isosteres of ellipticine whose biological activities are well established. To evaluate the anticancer potential of these pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amine derivatives in the human neuroblastoma cell line, the cytotoxicity was examined using the WST-1 assay after 72 h drug exposure. A clonogenic assay was used to assess the ability of treated cells to proliferate and form colonies. Protein expressions (Bax, bcl-2, cleaved caspase-3, cleaved PARP-1) were analyzed using Western blotting. The colony number decrease in cells was 50.54%, 37.88% and 27.12% following exposure to compounds 2d, 2g and 4b respectively at 10 μM. We also show that treating the neuroblastoma cell line with these compounds resulted in a significant alteration in caspase-3 and PARP-1 cleavage.

scholarly journals Synthesis and Bioinformatic Characterization of New Schiff Bases with Possible Applicability in Brain Disorders

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4160
Author(s):  
Speranta Avram ◽  
Ana Maria Udrea ◽  
Diana Camelia Nuta ◽  
Carmen Limban ◽  
Adrian Cosmin Balea ◽  
...  
Keyword(s):  
Schiff Bases ◽  
Neurodegenerative Disorders ◽  
Aromatic Aldehydes ◽  
Brain Disorders ◽  
Ir And Nmr Spectroscopy ◽  
Bioinformatics Tools ◽  
Ft Ir ◽  
New Treatments ◽  
New Compounds

(1) Background: The research aims to find new treatments for neurodegenerative diseases, in particular, Alzheimer’s disease. (2) Methods: This article presents a bioinformatics and pathology study of new Schiff bases, (EZ)-N′-benzylidene-(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide derivatives, and aims to evaluate the drug-like, pharmacokinetic, pharmacodynamic and pharmacogenomic properties, as well as to predict the binding to therapeutic targets by applying bioinformatics, cheminformatics and computational pharmacological methods. (3) Results: We obtained these Schiff bases by condensing (2RS)-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide with aromatic aldehydes, using the advantages of microwave irradiation. The newly synthesized compounds were characterized spectrally, using FT-IR and NMR spectroscopy, which confirmed their structure. Using bioinformatics tools, we noticed that all new compounds are drug-likeness features and may be proposed as potentially neuropsychiatric drugs (4) Conclusions: Using bioinformatics tools, we determined that the new compound 1e had a high potential to be used as a good candidate in neurodegenerative disorders treatment.

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