Synthesis, antitumor activities and functional mechanism of purine derivatives harboring phenyl moieties through three carbon bridges
AbstractA series of 2,6-diamine-9H-purine derivatives substituted with phenyl groups at the 8-position through three carbon bridges were synthesized as nonclassical antifolates. The anti-proliferative activities of these compounds against HL60, HeLa and A549 cells were tested. The inhibitory activities against rhDHFR and behavior towards thymine synthase (TS) and aminoimidazole carbonamide ribonucleotide transformylase (AICARFT) of our target compounds were determined. Compound4e displayed the best inhibitory activity against HL-60 and HeLa cells. Flow cytometry studies indicated that HL-60 cells treated with4e displayed S...
Source: Medicinal Chemistry Research - February 24, 2023 Category: Chemistry Source Type: research
Novel imino-thiazoloquinoxaline derivatives against renal cell carcinoma: less radiation-damaging approach
AbstractRenal cell carcinoma (RCC) is the most fatal tumor in the urinary system. Resistance development and unmet effective responses, request new anticancer agents with better therapeutic index. Ten new imino-thiazolo-quinoxaline derivatives (5a-j) were synthesized and preliminary evaluated for downregulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) activity taking sorafenib as a reference drug. Compounds5d&5h showed potent inhibition to VEGFR-2 activity at IC50 89.35 nM& 60.64 nM, respectively, then they both were further evaluated in-vitro against urinary bladder cancer cell line T-24 ta...
Source: Medicinal Chemistry Research - February 24, 2023 Category: Chemistry Source Type: research
Antibacterial, antifungal activities and toxicity of new synthetic fatty acid salicylate esters
This study aiming to prepare new antibacterial and antifungal drugs, 24 new salicylate-fatty acids were designed and synthesized from fatty acids and salicylate derivatives and tested in vitro on several bacteria and fungi strains. It was found that salicylates covalently linked to palmitic acid had the best results with good (MIC = 31.25 μg/ml) and moderate (MIC = 62.5 and 125 μg/ml) antibacterial and antifungal activity againststreptococcus pneumoniae,Staphylococcus aureus,Salomonella typhi,klebsiella pneumoniae,Escherichia coli,Trichophyton mentagrophytes,Microsporum audouinii,Epidermophyton floccosum and...
Source: Medicinal Chemistry Research - February 20, 2023 Category: Chemistry Source Type: research
Synthesis, α-glucosidase inhibitory activity, and molecular docking of cinnamamides
AbstractSuitably substituted cinnamamides (3a-n) were successfully synthesized and tested for α-glucosidase inhibitory activity. Nine of the synthesized cinnamamides (3a-f, k-m) displayed moderate inhibitory activity, which was better than acarbose (IC50 = 185.00 ± 9.4 µM), with IC50 values ranging from 44.43 ± 5.7 to 91.14 ± 11.4 µM. Their α-glucosidase inhibitory activity greatly depended on their structure with electron-withdrawing groups on the cinnamoyl aromatic ring causing increased inhibition activity. According to the in vitro assay results, compound3b withp-dimethylamino on the cinnamo...
Source: Medicinal Chemistry Research - February 16, 2023 Category: Chemistry Source Type: research
Design, synthesis and α-glucosidase inhibition study of novel pyridazin-based derivatives
AbstractIn this paper, pyridazin derivatives containing different thiobenzyl moieties were synthesized and screened for their inhibitory activities against rat intestinal α-glucosidase enzyme. The final products were easily obtained without the need to harsh purification steps. The in vitro results revealed that all the synthesized compounds were more potent (IC50s = 26.3–148.9 μM) than the clinically used drug, acarbose. The kinetic study revealed the competitive inhibition behavior of compound5m (Ki = −56 μM). Docking studies showed imperative interactions such as hydrogen bonding, Pi-Pi T-shaped, and P...
Source: Medicinal Chemistry Research - February 15, 2023 Category: Chemistry Source Type: research
Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids
AbstractFifteen novel butyric ester tethered dihydroartemisinin-isatin hybrids4a-d and5a-k were designed, synthesized, and evaluated for cytotoxicity against four human breast cancer cell lines, including MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR using the MTT method. A significant part of them were active against the four tested cancer cell lines, and the representative hybrid5b (IC50: 1.27 µM) was 14.88 -> 78.74 times more active than adriamycin (IC50: 18.90 µM), DHA (IC50: 28.28 µM) and ART (IC50: > 100 µM) against MCF-7 breast cancer cells, whereas hybrid5c (IC50: 2.39 and 3.95 ...
Source: Medicinal Chemistry Research - February 14, 2023 Category: Chemistry Source Type: research
Screening a small hydrazide-hydrazone combinatorial library for targeting the STAT3 in monocyte-macrophages with insulated reporter transposons
AbstractThe Signal Transducer and Activator of Transcription 3 (STAT3) pharmacological targeting is regarded as a prospective approach to treat cancer, autoimmune disorders, or inflammatory diseases. We have developed a series of reporters of the STAT3, NF- κB, Nrf2, metal-responsive transcription factor-1 (MTF-1), and hypoxia-inducible factor 1α (HIF-1α) transcriptional activation in human monocyte-macrophage line THP-1. The reporter lines were employed to test a set of hydrazide-hydrazones as potential STAT3 inhibitors. A hydrazide-hydrazone libra ry composed of 70 binary combinations of 7 carbonyl and 10 hydrazide co...
Source: Medicinal Chemistry Research - February 13, 2023 Category: Chemistry Source Type: research
Synthesis of nitrogen-containing oleanolic acid derivatives as carbonic anhydrase and acetylcholinesterase inhibitors
In this study, a total of 13 compounds(5–17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds(10, 11, 12, 15 and17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. ...
Source: Medicinal Chemistry Research - February 13, 2023 Category: Chemistry Source Type: research
The emerging role of proteolysis targeting chimeras (PROTACs) in the treatment of Alzheimer ’s disease
This article covers a recent update on designing of PROTACs using different linkers, their mechanism of action, pharmacokinetics, in addition to advantages and disadvantages of PROTACs as therapeutic modalities to treat AD.Graphical Abstract (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - February 9, 2023 Category: Chemistry Source Type: research
Recent advances on biologically active coumarin-based hybrid compounds
AbstractCoumarin hybrids have been designed and synthesized as an important new strategy in the field of medicinal chemistry. Coumarin core has been shown to form various compounds to combat several diseases including microbial, cancer, inflammatory, and neurodegenerative disorders. Recently, a number of coumarin-based drugs (e.g., coumadin, acenocoumarol, dicoumarol, phenprocoumon, and novobiocin) have been FDA-approved and are in the clinic, and several coumarin-containing compounds are in clinical trials. Our group classified coumarin-based hybrid compounds into groups showing shared biological activities and discussed ...
Source: Medicinal Chemistry Research - February 9, 2023 Category: Chemistry Source Type: research
DNA sequence-specific ligands. XX. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric trisbenzimidazoles DB3P(n)
AbstractA new series of AT-specific minor groove DNA ligands (DB3P(n);n = 1,2,3,4) was synthesized and their spectral, biological and virological properties were investigated. With a methylene spacers of different lengths blocks of three AT pairs located at different distances from each other could be recognized. The compounds synthesized suppressed the activity of HIV-1 integrase at submicromolar concentrations (0.25–0.50 µМ). Also, DB3P(n) were found to be effective inhibitors of simplex virus type I and DNA topoisomerase I. The synthesized DB3P(n) demonstrated good solubility in water, could penetrate through ...
Source: Medicinal Chemistry Research - February 3, 2023 Category: Chemistry Source Type: research
Asciminib: first FDA approved allosteric inhibitor of BCR-ABL1 for the treatment of chronic myeloid leukemia
AbstractChronic myelogenous leukemia (CML), a type of cancer of the white blood cells, arises due to the constitutive activity of the BCR-ABL1 oncoprotein. Several non-specific ATP competitive tyrosine kinase inhibitors including imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif) can enhance the overall survival rate of CML patients. However, many of these drugs became resistant due to mutation of the threonine T315 to isoleucine (T315I). Asciminib binds myristate pocket in an allosteric site, outside the catalytic/ATP-binding site. It inhibits both wide- type and mutated T315I BCR-ABL1 a...
Source: Medicinal Chemistry Research - February 2, 2023 Category: Chemistry Source Type: research
New tetracyclic systems integrated thienopyridine scaffold as an anti-dementia lead: in silico study and biological screening
AbstractAlzheimer ’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones of anti-dementia drugs. Accordingly, novel series of hexahydrobenzothienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta(thienoquinoline/thienodipyridine), and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagent, e.g. cyclohexanones, cyclopentanone, and 1-methyl-piperidin-4-one to afford 14 ne...
Source: Medicinal Chemistry Research - February 1, 2023 Category: Chemistry Source Type: research
Design, synthesis and anti-TB and anti-bacterial activity of Ciprofloxacin derivatives containing N-(amino)piperazine moieties
In this study, theN-(amino)piperazine moieties from rifamycins were incorporated into the ciprofloxacin core according to the hybrid strategy, and different substituents were introduced to theN-(amino)piperazine to explore their influence to the anti-TB and antibacterial potency. Compounds1k with cyclohexyl group (MIC = 0.28 μM) and3e withN-methyl-N-isopropyl (MIC = 0.60 μM) group showed comparable anti-TB activity to CPFX (MIC = 0.34 μM). Compound1d (MIC = 2～8 μg/mL) was 4～> 32 fold more potent than CPFX (MIC = 16～> 64 μg/mL) against MRSA and VREE.fm. Currently, comp...
Source: Medicinal Chemistry Research - January 31, 2023 Category: Chemistry Source Type: research
Novel benzenesulfonamide bearing 1,2,4-triazoles as potent anti-microbial and anti-oxidant agents
AbstractA series comprising 30 novel benzenesulfonamide bearing 1,2,4-triazoles1a–1h,2a–2h,3a–3h,4b–4f and4h has been synthesized and investigated as anti-microbial and anti-oxidant agents. All the tested compounds exhibited moderate to excellent inhibitory potential against tested Gram-positive (Staphylococcus aureus ATCC 6538P, Listeria monocytogenes MTCC 657, andBacillus cereus ATCC 11770) and Gram-negative (Pseudomonas aeruginosa ATCC 15442, Escherichia coli MTCC 143, Salmonella typhi MTCC 733, Shigella flexneri ATCC 9199) bacterial strains with minimum inhibitory concentration values ranging from 3.12 to 12.5 ...
Source: Medicinal Chemistry Research - January 30, 2023 Category: Chemistry Source Type: research
