Rationale Design, Synthesis And <i>In Vitro</i> Anticancer Activity of New 2,5‐Disubstituted‐1,3,4‐Oxadiazole Analogues

Ahsan, Mohamed Jawed

doi:10.1002/slct.201600465

Cited by 12 publications

(13 citation statements)

References 34 publications

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“…Among the different isomers, 1,3,4-oxadiazole isomer shows a lots of therapeutic activities like antibacterial [9,10], anticonvulsant [11], antitumor [12][13][14][15][16][17][18][19][20][21][22], hypoglycemic, antipyretic [23], anti-tubercular [10,24], anti-viral [25], immunosuppressive, spasmolytic, antioxidant [13,26], anti-inflammatory [23,27,28], insecticidal [20], CNS stimulant, ant amoebic, antiemetic, antidepressant, anthelmintic activities, vasodilator activity, antimycotic activity [29], anti-allergic, anti-Alzheimer activity, ulcerogenic and antihypertensive activities etc.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of oxadiazole or furadiazole containing compounds

Siwach

Verma

2020

BMC Chemistry

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As we know that, Oxadiazole or furadi azole ring containing derivatives are an important class of heterocyclic compounds. A heterocyclic five-membered ring that possesses two carbons, one oxygen atom, two nitrogen atoms, and two double bonds is known as oxadiazole. They are derived from furan by the replacement of two methylene groups (= CH) with two nitrogen (-N =) atoms. The aromaticity was reduced with the replacement of these groups in the furan ring to such an extent that it shows conjugated diene character. Four different known isomers of oxadiazole were existed such as 1,2,4-oxadiazole, 1,2,3-oxadiazole, 1,2,5-oxadiazole & 1,3,4-oxadiazole. Among them, 1,3,4-oxadiazoles & 1,2,4-oxadiazoles are better known and more widely studied by the researchers due to their broad range of chemical and biological properties. 1,3,4-oxadiazoles have become important synthons in the development of new drugs. The derivatives of the oxadiazole nucleus (1,3,4-oxadiazoles) show various biological activities such as antibacterial, anti-mycobacterial, antitumor, anti-viral and antioxidant activity, etc. as reported in the literature. There are different examples of commercially available drugs which consist of 1,3,4-oxadiazole ring such as nitrofuran derivative (Furamizole) which has strong antibacterial activity, Raltegravir as an antiviral drug and Nesapidil drug is used in anti-arrhythmic therapy. This present review summarized some pharmacological activities and various kinds of synthetic routes for 2, 5-disubstituted 1,3,4-oxadiazole, and their derived products.

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Section: Introductionmentioning

confidence: 99%

Therapeutic potential of oxadiazole or furadiazole containing compounds

Siwach

Verma

2020

BMC Chemistry

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“…The synthetic protocol is summarized in Scheme 1 . The intermediates 2a , and 2b–c were prepared using the methods described elsewhere [ 34 , 35 ]. The structure of curcumin analogues ( 3a–c ) were confirmed by spectroscopic techniques.…”

Section: Resultsmentioning

confidence: 99%

“…An equimolar mixture of curcumin ( 1 ) (1 mmol; 368 mg) and N-(2-methoxyphenyl)-hydrazine carboxamide ( 2a ) (1 mmol; 181 mg) in glacial acetic acid was stirred continuously at 80 °C in a sand bath for 10 h. The reaction mixture was then concentrated under a vacuum to remove excess solvent before being poured into crushed ice, filtered, dried, and recrystallized with ethanol to yield the compound 3a . The intermediate 2a was prepared as per the reported method in two steps starting from o-anisidine [ 34 ]. Method A used glacial acetic acid as a solvent, whereas Method B used a green solvent system glycerol-water (1:2), which was found to be faster and yielded slightly more.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, DFT Analyses, Antiproliferative Activity, and Molecular Docking Studies of Curcumin Analogues

Ahsan¹,

Choudhary²,

Ali

et al. 2022

Plants

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With 19.3 million new cases and almost 10 million deaths in 2020, cancer has become a leading cause of death today. Curcumin and its analogues were found to have promising anticancer activity. Inspired by curcumin’s promising anticancer activity, we prepared three semi-synthetic analogues by chemically modifying the diketone function of curcumin to its pyrazole counterpart. The curcumin analogues (3a–c) were synthesized by two different methods, followed by their DFT analyses to study the HOMO/LUMO configuration to access the stability of compounds (∆E = 3.55 to 3.35 eV). The curcumin analogues (3a–c) were tested for antiproliferative activity against a total of five dozen cancer cell lines in a single (10 µM) and five dose (0.001 to 100 µM) assays. 3,5-Bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxy)ethanone (3b) and 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(2,4-dichlorophenoxy)ethanone (3c) demonstrated the most promising antiproliferative activity against the cancer cell lines with growth inhibitions of 92.41% and 87.28%, respectively, in a high single dose of 10 µM and exhibited good antiproliferative activity (%GIs > 68%) against 54 out of 56 cancer cell lines and 54 out of 60 cell lines, respectively. The compound 3b and 3c demonstrated the most potent antiproliferative activity in a 5-dose assay with GI50 values ranging between 0.281 and 5.59 µM and 0.39 and 0.196 and 3.07 µM, respectively. The compound 3b demonstrated moderate selectivity against a leukemia panel with a selectivity ratio of 4.59. The HOMO-LUMO energy-gap (∆E) of the compounds in the order of 3a > 3b > 3c, was found to be in harmony with the anticancer activity in the order of 3c ≥ 3b > 3a. Following that, all of the curcumin analogues were molecular docked against EGFR, one of the most appealing targets for antiproliferative activity. In a molecular docking simulation, the ligand 3b exhibited three different types of interactions: H-bond, π-π-stacking and π-cationic. The ligand 3b displayed three H-bonds with the residues Met793 (with methoxy group), Lys875 (with phenolic group) and Asp855 (with methoxy group). The π-π-stacking interaction was observed between the phenyl (of phenoxy) and the residue Phe997, while π-cationic interaction was displayed between the phenyl (of curcumin) and the residue Arg841. Similarly, the ligand 3c displayed five H-bonds with the residue Met793 (with methoxy and phenolic groups), Lys845 (methoxy group), Cys797 (phenoxy oxygen), and Asp855 (phenolic group), as well as a halogen bond with residue Cys797 (chloro group). Furthermore, all the compound 3a–c demonstrated significant binding affinity (−6.003 to −7.957 kcal/mol) against the active site of EGFR. The curcumin analogues described in the current work might offer beneficial therapeutic intervention for the treatment and prevention of cancer. Future anticancer drug discovery programs can be expedited by further modifying these analogues to create new compounds with powerful anticancer potentials.

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“…The completion of the reaction was monitored throughout by preparatory thin layer chromatography (TLC Silica gel 60 F 254 ) in the mobile phase n-hexane: ethylacetate (6: 4). The substituted phenyl urea (( B1-B3 ) was prepared as per the reported method [ 41 , 42 ]. Curcumin exhibits tautomeric isomerism viz.…”

Section: Resultsmentioning

confidence: 99%

Chemical Modification of Curcumin into Its Semi-Synthetic Analogs Bearing Pyrimidinone Moiety as Anticancer Agents

Afzal

Yusuf

Ahsan³

et al. 2022

Plants

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Natural products (NPs) continue to provide a structural template for the design of novel therapeutic agents and expedite the drug discovery process. The majority of FDA-approved pharmaceuticals used in medical practice can be traced back to natural sources, and NPs play a significant role in drug development. Curcumin, one of the most well-studied chemicals among the NPs, is currently the subject of intense investigation for its biological effects, including the prevention and treatment of cancer. Cancer has overtaken all other causes of death in the world today, with 19.3 million new cases and nearly 10 million deaths predicted in 2020. In the present investigation, we reported the synthesis of three semi-synthetic analogues of curcumin-bearing pyrimidinone moiety by the chemical modification of the diketone function () of curcumin followed by their characterization by analytical techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data. According to the National Cancer Institute (NCI US) methodology, the curcumin analogues (C1-C3) were tested for their anticancer efficacy against 59 cancer cell lines in a single dose assay. 1-(2,6-Dichlorophenyl)-4,6-bis((E)-4-hydroxy-3-methoxystyryl)pyrimidin-2(1H)-one (C2) demonstrated the most promising anticancer activity with mean percent growth inhibition (%GIs) of 68.22 in single dose assay at 10 µM. The compound exhibited >68 %GIs against 31 out of 59 cancer cell lines and was found to be highly active against all leukemia and breast cancer cell lines. The compound C2 showed a lethal effect on HT29 (colon cancer) with %GI of 130.44, while 99.44 %GI was observed against RPMI-8226 (Leukemia). The compound C2 displayed better anticancer activity against the panels of CNS, melanoma, ovarian, prostate, and breast cancer cell lines than curcumin and other anti-EGFR agents gefitinib and imatinib in single dose assay. The compound C2 also demonstrated potent anticancer activity in a 5-dose assay (0.001 to 100 µM) with GI50 values ranging from 1.31 to 4.68 µM; however, it was found to be non-selective with SR values ranging from 0.73 to 1.35. The GI50 values of compound C2 were found to be better than that of the curcumin against all nine panels of cancer cell lines. All of the curcumin analogues were subsequently investigated for molecular docking simulation against EGFR, one of the most attractive targets for antiproliferative action. In molecular docking studies, all the ligands were found to accommodate the active site of EGFR and the binding affinity of ligand C2 was found to be −5.086 kcal/mol. The ligand C2 exhibited three different types of interactions: H-bond (Thr790 and Thr854), π-cationic (Arg841), and aromatic H-bond (Asn842). The curcumin analogues reported in the current investigation may provide valuable therapeutic intervention for the prevention and treatment of cancer and accelerate anticancer drug discovery programs in the future.

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Rationale Design, Synthesis And In Vitro Anticancer Activity of New 2,5‐Disubstituted‐1,3,4‐Oxadiazole Analogues

Cited by 12 publications

References 34 publications

Therapeutic potential of oxadiazole or furadiazole containing compounds

Therapeutic potential of oxadiazole or furadiazole containing compounds

Synthesis, DFT Analyses, Antiproliferative Activity, and Molecular Docking Studies of Curcumin Analogues

Chemical Modification of Curcumin into Its Semi-Synthetic Analogs Bearing Pyrimidinone Moiety as Anticancer Agents

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