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![Fig. 1. Anticancer cyclic pentapeptide X [19].](publication/273486278/figure/fig1/AS:283281594568704@1444551003476/Anticancer-cyclic-pentapeptide-X-19_Q320.jpg)
![Scheme 2. Synthetic routes for macrocyclic calix[4]arene 7.](publication/273486278/figure/fig2/AS:669333818712079@1536593026734/Scheme-2-Synthetic-routes-for-macrocyclic-calix4arene-7_Q320.jpg)
Novel macrocyclic dipicolinic acid acylated peptides based on upper rim bridged peptido-calix[4]arenes, peptido-pyridines or hybrid structures of both, were synthesized as potential molecu-lar metallacages and chemosensors. While conventional azide or mixed anhydride (ethyl chlorofor-mate) peptide couplings served well for assembling the L-tyrosine...
Citations
... Although Tröger base and its analogues have attracted interest of many researcher groups due to their fascinating structures and properties (Yuan, et al., 2011), however, attention has been inadequately focused on these compounds from the biological point of view (Bailly, et al., 2000;Baldeyrou, et al., 2002;Manda, et al., 2014;Yang, et al., 2015). In addition, some of macrocyclic hetero-nitrogen derivatives have been synthesized (Abu-Ghalia, et al., 2012;Amr, et al., 2019;Naglah, et al., 2020) and have shown promising biological activity, i.e. analgesic and anticonvulsant (Amr, 2005), antimicrobial (Amr, et al., 2006;Azab, et al., 2016), anti-proliferative, 5α-reductase inhibiting (Alanazi, et al., 2020), pharmacological (Al Thagfan, et al., 2018), anticancer , as well as biological activities (Khayyat and Amr, 2014). In view of these observations and in continuation of our previous work in macrocyclic chemistry, we synthesized some new Trögerophane derivatives and tested their anticancer activities. ...
1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.
... Furthermore, peptides constitute a major class of important anticancer therapeutic agents [7]. Chemically synthesized peptides have been reported to exhibit antimicrobial, anti-inflammatory [8][9][10][11][12][13][14][15][16], as well as anticancer properties [17][18][19][20][21]. We have previously explored the analytical and biological characteristics of some bis-amino acid and peptide conjugates of dipicolinic acid [22]. ...
A series of macrocyclic pyrido-pentapeptide candidates 2–6 were synthesized by using N,N-bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine 1a,b as starting material. Structures of the newly synthesized compounds were established by IR, 1H and 13C-NMR, and MS spectral data and elemental analysis. The in-vitro cytotoxicity activity was investigated for all compounds against MCF-7 and HepG-2 cell lines and the majority of the compounds showed potent anticancer activity against the tested cell lines in comparison with the reference drugs. Out of the macrocyclic pyrido-pentapeptide based compounds, 5c showed encouraging inhibitory activity on MCF-7 and HepG-2 cell lines with IC50 values 9.41 ± 1.25 and 7.53 ± 1.33 μM, respectively. Interestingly, 5c also demonstrated multitarget profile and excellent inhibitory activity towards VEGFR-2, CDK-2 and PDGFRβ kinases. Furthermore, molecular modeling studies of the compound 5c revealed its possible binding modes into the active sites of those kinases.
... Several hydrazide– hydrazone derivatives have shown antimicrobial, antiviral, antimalarial, anticonvulsant, antiinflammatory, antituberculosis, antitumor, antiplatelet aggregation, antileishmanial, analgesic and antimalarial properties[4][5][6][7][8][9][10][11][12]. Furthermore, various substituted pyridines were recorded to exhibit antibacterial, anti-inflammatory and antitumor activity[13][14][15]. In the title compound, the asymmetric unit contains only one independent molecule. ...
C15H23N7O4, orthorhombic, Aba2, a = 18.4956(11) Å, b = 23.9806(16) Å, c = 8.1572(5) Å, V = 3618.0(4) ų, Z = 8, Rgt(F) = 0.0521, wRref(F²) = 0.1144, T = 293(2) K.
... The conversion of these active peptides into peptidomimetics has been a successful approach for making new biologically active compounds [5]. In addition, the synthesis of some new macrocyclic compounds from pyridinedicarboxylic acid with selected amino acids and screening of their biological activities were reported [6][7][8][9][10][11]. On the other hand, the synthesis of chemosensors is an interesting approach providing accurate analytical tools in different analytical fields. ...
... Synthesis of some new potential bis-intercallators based on chiral pyridine-2,6dicarboxamides was equally reported [24]. In view of these observations and as continuation of our previous work [6][7][8][9][10][11][12][13][14][15][16][17][18][19] in macrocyclic and heterocyclic chemistry, we have synthesized some new linear and macrocyclic peptides containing amino acid and pyridine moieties and some of the synthesized compounds were screened for their antimicrobial, anti-inflammatory and anticancer activities compared to the reference drugs. ...
A series of linear and macrocyclic peptides 3-12 were synthesized using 3,5-pyridinedicarboxylic acid (1) as starting material and screened for their antimicrobial, anti-inflammatory and anticancer activities. Bis-ester 3 was prepared from 1 and L-leucine methyl ester. Hydrazinolysis and hydrolysis of dipeptide methyl ester 3 with hydrazine hydrate or 1 N sodium hydroxide afforded compounds 4 and 5, respectively. Cyclization of the dipeptide 5 with L-lysine methyl ester afforded cyclic pentapeptide ester 6. Compounds 7-9 were synthesized by reacting hydrazide 4 with phthalic anhydride, 1,8-naphthalene anhydride or acetophenone derivatives. Treatment of acid hydrazide 4 with aromatic aldehydes or tetraacid dianhydrides afforded the corresponding bis-dipeptide hydrazones 10a-e and macrocyclic peptides 11 and 12, respectively. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, biological and pharmacological activities of the synthesized compounds was reported.
... On the other hand, peptides rarely function well as drugs due to their low bioavailability and rapid degradation within cells [9]. In our previous work, we reported the synthesis of some macrocyclic candidates from the reactions of dipicolinic acid with amino acids and their biological activity screening1011121314. In particular, 2,6-peptidopyridines exhibited a general ionophoric potency [15] and were used for inventing novel thiocyanate-selective membrane sensors [16]. ...
... In our previous work, a series of chiral macrocyclic compounds were synthesized using macrocyclic bishydrazide derivative 3 [13], which was obtained from the corresponding ester 2 according to the published procedure [23,24] (Scheme 1). Condensation in refluxing acetic acid of hydrazide 3 with selected acid anhydrides, namely 1,8-naphthalic anhydride, phthalic anhydride or 2,3,4,5-tetrachlorophthalic anhydride, afforded the corresponding tricyclobisdiimide derivatives 4 and 5a,b, respectively (Table 1). ...
... TLC (silica gel, aluminum sheets 60F 254 , Merck, Darmstadt, Germany) was used for tracing the reactions. The starting material 3 was prepared according to the reported procedure [13] (Scheme 1). Antimicrobial screening was carried out in Department of Microbial Chemistry, National Research Center, Cairo, Egypt. ...
A series of macrocyclic imides and Schiff-bases have been prepared via the cyclocondensation of pyridine-2,6-dicarbonyl dichloride (1) with L-ornithine methyl ester to give the corresponding macrocyclic bisester 2. Treatment of 2 with hydrazine hydrate gave macrocyclic bisacid hydrazide 3, which was used as starting material. Condensation of bishydrazide 3 with diacid anhydrides or aromatic aldehydes in refluxing acetic acid or ethanol gave the corresponding macrocyclic bisimides 4, 5a,b and macrocyclic bis- hydrazones 6a-j, respectively. The structure assignments of the new compounds were based on chemical and spectroscopic evidence. The antimicrobial screening showed that many of these newly synthesized compounds have good antimicrobial activities, comparable to ampicillin and ketaconazole used as reference drugs.
... Also, Schiff base and other heterocyclic derivatives were reported to possess diverse biological activities, such as antibacterial78910 and anti-inflammatory111213 properties. In addition, several substituted pyridines and their derivatives were reported to exhibit significant antimicrobial [14], anti-inflammatory [15] and anticancer activities [16]. In continuation of our interest in the chemical and pharmacological properties of disubstituted pyridine derivatives17181920, we report herein the synthesis and antimicrobial activities of a new series of hydrazides and their corresponding N 2 ,N 6 -bis(1-oxo-1-(2- (substituted-benzylidene)-hydrazinyl)propan-2-yl)pyridine-2,6-di-carboxamide derivatives (Schiff's bases). ...
A series of pyridine-bridged 2,6-bis-carboxamide Schiff's bases has been prepared starting from 2,6-pyridinedicarbonyl dichloride (1) and L-alanine or 2-methyl-alanine methyl ester.The coupling of acid chloride 1 with L-alanine methyl ester hydrochloride -or 2-methylalanine methyl ester hydrochloride gave the corresponding 2,6-bis-carboxamide pyridine methyl esters 2a,b.Hydrazonolysis of 2 with hydrazine hydrate afforded the corresponding bis-hydrazides 3a,b. Treatment of 3a,b with appropriate aromatic or heterocyclic aldehydes afforded the corresponding pyridine- bridged 2,6-bis-carboxamide Schiff's bases 4a-f and 5a-f, respectively. The newly synthesized compounds 2-5 were screened for their bactericidal and fungicidal activities. Many of the obtained compounds exhibited significant antimicrobial activity, comparable to streptomycin and fusidic acid, which were used as reference antibiotic drugs.
As important cancer therapeutic agents, macrocyclic peptides have recently drawn great attention, mainly because they are synthetically accessible and have lower toxicity towards normal cells. In the present work, we synthesized newly macrocyclic pyridoheptapeptide derivatives. The synthesized derivatives were characterized using standard chemical and spectroscopic analytical techniques, and their anticancer activities against human breast and hepatocellular cancer cells were investigated. Results showed that compounds 1a and 1b were the most effective against hepatocellular (HepG2) and breast (MCF-7) cancer cell lines, respectively.
A series of branched tetrapeptide Schiff bases 3–6 were designed and synthesized from corresponding tetrapeptide hydrazide 2 as a starting material.In vitroevaluation of the synthesized compounds 4–6 against breast MCF-7 carcinoma cells identified their excellent anticancer potency, with IC50 ranging from 8.12 ± 0.14 to 17.55 ± 0.27 μM in comparison with the references, cisplatin and milaplatin (IC50= 13.34 ± 0.11and 18.43 ± 0.13 μM, respectively). Furthermore, all derivatives demonstrated promising activity upon evaluation of theirin vitroandin vivosuppression of p53 ubiquitination and inhibition assessment for LDHA kinase. Finally, molecular docking studies were performed to predict the possible binding features of the potent derivatives within the ATP pocket of LDHA in an attempt to get a lead for developing a more potent LDHA inhibitor with anti-proliferative potency.
New pyridine-2,6-dicarboxamide derivatives containing sulfonamide groups were synthesized by the coupling of pyridine-2,6-dicarbonyl dichloride and various aminobenzenesulfonamides in a mixture of dichloromethane and acetone. The pyridinedicarboxamide-based sulfonamides were evaluated as carbonic anhydrase (CA) and cholinesterase (ChE) inhibitors, and they showed IC50 values in the ranges 12.8–37.6 nM against human carbonic anhydrase I (hCA I), 17.8–46.7 nM against human carbonic anhydrase II (hCA II), 98.4–197.5 nM against acetylcholinesterase (AChE), and 82.2–172.7 nM against butyrylcholinesterase (BuChE). These results are comparable with those for known inhibitors such as acetazolamide (IC50 = 32.1 nM for hCA I and IC50 = 51.0 nM for hCA II) and rivastigmine (IC50 = 60.2 nM for AChE and IC50 = 14.0 nM for BuChE), which qualifies the synthesized compounds as candidates for a more in-depth study.
