Anticancer Activities of Newly Synthesized Chiral Macrocyclic Heptapeptide Candidates.

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.

Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors.

A series of macrocyclic pyrido-pentapeptide candidates ⁻ were synthesized by using ,-bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine , as starting material. Structures of the newly synthesized compounds were established by IR, ¹H and C-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.

Synthesis of new (Nalpha-dipicolinoyl)-bis-L-valyl-L-phenylalanyl linear and macrocyclic bridged peptides as anti-inflammatory agents.

In continuation to our search for new chiral macrocyclic peptide-based anti-inflammatories, the suggestion, synthesis, structure elucidation of some Nalpha-bis-dipicolinoyl amino acids, linear, tetra and cyclic (penta and octa)-bridged peptides 3-10, were realized herein. The newly synthesized compounds showed potent anti-inflammatory activity with low toxicity (LD50) comparable to indomethacin and diclofenac as reference anti-inflammatory drugs.

Synthesis and investigation of a new cyclo (Nalpha-dipicolinoyl) pentapeptide of a breast and CNS cytotoxic activity and an ionophoric specificity.

A new acylated cyclopentapeptide namely, Cyclo-( N(alpha)-dipicolinoyl)- bis-[ L-Leu-DL-Nval]- L-Lys OMe (5) was suggested and synthesized. The structural conception of 5 was rationalized by analogy to the structural features of some known cyclodepsipeptides exemplified by the antibiotic and DNA intercalator actinomycin D (NSC: 3053), the ionophore and anti-HIV enniatin B (NSC: 692895) and the ionophore and antibiotic valinomycin (NSC: 630175). The cyclopeptide 5 was chemically synthesized, starting from its linear tetrapeptide ester precursor 2 by coupling L-lysine methyl ester to the prepared tetrapeptide acid 3 or hydrazide 4 via the mixed anhydride or azide method, respectively.

Optimized conventional synthesis of "RGD" and "RGDS" peptides and their sarcosine mimics as integrin GP IIb/IIIa antagonists.

Synthetic arginyl-glycyl- alpha-aspartyl "RGD" and arginyl-glycyl- alpha-aspartyl-serinyl "RGDS" peptide sequences, which are originally located in matrix proteins, are confirmed to be as versatile integrin GP IIb/IIIa antagonists. Since integrins, as cell surface glycoprotein receptors are implicated in several physiological mechanisms, these peptides are recently specially considered in the design of new therapeutics. Replacing glycine by sarcosine, as its more lipophilic isomer, in RGD peptides seemed, accordingly, interesting in revealing some structural/biological activity relationships.

Synthesis of a new antischistosomally active and toxicologically tolerant C-12 monothione surrogate of the universal antihelmintic praziquantel.

A new C-12 monothione mimic (III) of the universal antihelmintic Praziquantel (I) namely, 2-cyclohexylthiocarbonyl( 1,2.3,6,7,11b)-hexahydro-4H-pyrazino[2-1a] isoquinoline-4-one was chemically synthesized and structurally elucidated (Elemental analysis. El-Mass, 13C-NMR and IR spectroscopy).

Synthesis and study of the antischistosomal potency and induced biological parameters of a new 2-palmitoyl analogue of the universal antihelminthic praziquantel.

2-Palmitoyl[1,2,3,6,7,11b]hexahydro-4H-pyrazino[2-la]isoquinoline-4-one [III] a highly lipophilic analogue of the universal antihelminthic PRAZIQUANTEL [I] was rationally multi-stepwise synthesized and antischistosomally and biochemically screened. The 2-palmitoyl conjugation was hypothesized to be an antischistosomal adjuvant (Tween 40 mimicry), to the reported crucial pyrazino-isoquinoline moiety. On a constant weight doses bases of I and III (500 mg/kg mouse body weight), the activity of III was found to be approximately 70% of I (mice infected with S.

Synthesis and anti-phlogistic potency of some new non-proteinogenic amino acid conjugates of "Diclofenac".

In search for more potent, particularly less ulcerogenic gastritis that hopefully replace the universal NSAID "Diclofenac", (2-[(2,6-dichlorophenyl)amino]-phenylacetic acid, C.A.S.

Synthesis and antischistosomal activity of a new 2-nicotinoyl dipeptide analogue of praziquantel.

As an approach to a structure-antischistosomal activity-relationship with possible pharmacological potentiation of the anthelmintic drug praziquantel, a new dipeptide analogue, namely, N alpha-nicotinoyl-L-aspartyl-beta-(1,2,3,6,7,11b-hexahydro-4H-pyrazino[2- 1a]isoquinoline-4-one)-L-phenylalanine methyl ester, was synthesized and antischistosomally investigated in mice infected with S. mansoni cercariae. Parallely, its simple 2-nicotinoyl analogue was synthesized and tested.

Synthesis of 3,5-disubstituted pyridines as antimicrobial agents.

3,5-Diacetylpyridine (1) reacted with hydroxylamine hydrochloride, thiourea or phenylhydrazine affording the corresponding carbaldoximo- (2) aminothiazolyl-(3) and phenylhydrazono- (4) derivatives, respectively. Cyclization of 4 by the action of PPA or thionyl chloride afforded the corresponding indolyl- (5) and thiadiazolyl-(6) derivatives. Condensation of 1 with aldehydes yielded bis-(beta-acryloyl) derivatives 7, which on further treatment with malononitrile or ethyl cyanoacetate afforded cyanopyridines of the types 8 and 9.

Synthesis of inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli.

In order to obtain inhibitors of the meso-diaminopimelate-adding enzyme, which participates in the biosynthesis of bacterial peptidoglycan, several N alpha-propionyl-dipeptides of the general formula Pr-L-Ala-ambo-Xaa-OH were synthesized. Xaa represented methionine S,S-dioxide, methionine S-oxide, methionine sulfoximine, and 2-amino-4-phosphonobutyric acid, i.e.

Specificity of the uridine-diphosphate-N-acetylmuramyl-L-alanyl-D-glutamate: meso-2,6-diaminopimelate synthetase from Escherichia coli.

To investigate the specificity of the uridine-diphosphate-N-acetylmuramyl-L-alanyl-D-glutamate: meso-2,6-diaminopimelate synthetase, various compounds mimicking more or less different parts of the UDP-MurNAc-L-Ala-D-Glu substrate were prepared. Their size ranged from that of uridine or L-Ala-D-Glu to that of the whole nucleotide substrate. Chemical synthesis led to N alpha-acyl-dipeptides, in which the acyl group mimicked the MurNAc moiety, and to glycopeptides MurNAc(alpha or beta-Me)-L-Ala-D-Glu, in which the anomeric function is blocked.