Design, synthesis, and biochemical and computational screening of novel oxindole derivatives as inhibitors of Aurora A kinase and SARS-CoV-2 spike/host ACE2 interaction
AbstractIsatin (indol-2,3-dione), a secondary metabolite of tryptophan, has been used as the core structure to design several compounds that have been tested and identified as potent inhibitors of apoptosis, potential antitumor agents, anticonvulsants, and antiviral agents. In this work, several analogs of isatin hybrids have been synthesized and characterized, and their activities were established as inhibitors of both Aurora A kinase and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike/host angiotensin-converting enzyme II (ACE2) interactions. Amongst the synthesized isatin hybrids, compounds6a,6f,6g, a...
Source: Medicinal Chemistry Research - March 5, 2024 Category: Chemistry Source Type: research
Bioassay-guided fractionations of Cannabis sativa extract and HPLC-assisted purifications of anti-proliferative active fractions lead to the isolation of 16 known and one new phytomolecule and their in-silico analysis
AbstractThe comprehensive anti-cancer activities of cannabinoid acids and non-cannabinoids are not fully explored. Herein we report simple extraction, faster bioassay-guided fractionation, and HPLC-assisted purification of bioactive secondary metabolite and their identification. Anti-proliferative activity of six cannabinoid acids and eleven non-cannabinoids from the leaves ofCannabis sativa was evaluated. HPLC- assisted purification from the bioactive fractions leads to isolate one new compound Methoxy Canniprene (methoxy isoprenyl bibenzyl), including all six CBDA ’s eleven non-cannabinoids in a single step, and NMR, H...
Source: Medicinal Chemistry Research - March 5, 2024 Category: Chemistry Source Type: research
Design, synthesis, and biochemical and computational screening of novel oxindole derivatives as inhibitors of Aurora A kinase and SARS-CoV-2 spike/host ACE2 interaction
AbstractIsatin (indol-2,3-dione), a secondary metabolite of tryptophan, has been used as the core structure to design several compounds that have been tested and identified as potent inhibitors of apoptosis, potential antitumor agents, anticonvulsants, and antiviral agents. In this work, several analogs of isatin hybrids have been synthesized and characterized, and their activities were established as inhibitors of both Aurora A kinase and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike/host angiotensin-converting enzyme II (ACE2) interactions. Amongst the synthesized isatin hybrids, compounds6a,6f,6g, a...
Source: Medicinal Chemistry Research - March 5, 2024 Category: Chemistry Source Type: research
Bioassay-guided fractionations of Cannabis sativa extract and HPLC-assisted purifications of anti-proliferative active fractions lead to the isolation of 16 known and one new phytomolecule and their in-silico analysis
AbstractThe comprehensive anti-cancer activities of cannabinoid acids and non-cannabinoids are not fully explored. Herein we report simple extraction, faster bioassay-guided fractionation, and HPLC-assisted purification of bioactive secondary metabolite and their identification. Anti-proliferative activity of six cannabinoid acids and eleven non-cannabinoids from the leaves ofCannabis sativa was evaluated. HPLC- assisted purification from the bioactive fractions leads to isolate one new compound Methoxy Canniprene (methoxy isoprenyl bibenzyl), including all six CBDA ’s eleven non-cannabinoids in a single step, and NMR, H...
Source: Medicinal Chemistry Research - March 5, 2024 Category: Chemistry Source Type: research
Synthesis and pharmacological activities of Schiff bases with some transition metal complexes: a review
AbstractSchiff bases transition metal complexes have received significant attentions in the scientific community for their versatile applications. The incorporation of metals to Schiff base ligands attracts much attention, since the metals and Schiff base ligands coordinated via bonding. Thus, chelation effects will enhance and improve the biological activities of the derivatives of title compound. Most of these derivatives displayed broad range bioactivities including antibacterial, antifungal, antituberclosis, antimalarial, antioxidant, antidiabetic, anti-inflammatory and anticancer activities. Up to date, continuous eff...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Selectivity of N(2)-substituted oxotriazinoindole aldose reductase inhibitors is determined by the interaction pattern with Pro301-Arg312 loop of aldehyde reductase
AbstractNovel oxotriazinoindoles (OTIs) were recently reported as highly efficient and selective aldose reductase inhibitors. Here, a series of novelN(2)-substituted oxotriazinoindoles was developed with the aim to investigate molecular interactions within the aldose reductase (ALR2) inhibitor binding site. About twice increased inhibition efficacy of the most efficient derivative14 (N(2)-CH2CH2COOH) compared to the unsubstituted leadOTI was obtained, yet at the expense of selectivity relative to anti-target aldehyde reductase (ALR1). To explain the major drop in selectivity, observed also in otherN(2)-substituted derivati...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Unveiling the potential of prodrug and drug-conjugate strategies in treatment of diabetes mellitus and its complications
AbstractThe 2021 statistics from the International Diabetes Federation reveals that approximately 537 million adults between the ages of 20 and 79 are currently coping with diabetes, highlighting the pressing demand for innovative treatments. To expedite this process, it is crucial to learn from previous failures in drug development. One established method for enhancing the biological, pharmacokinetic or the physicochemical properties of potent drug candidates is through the use of prodrugs. Prodrugs have demonstrated their effectiveness in surmounting challenges related to a drug ’s efficacy during the phases of drug re...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Benzocaine-N-acylindoline conjugates: synthesis and antiviral activity against Coxsackievirus B3
AbstractIndoline-5-sulfonamide derivatives of benzocaine have been synthesized using a sequence of three reactions:N-acylation, sulfochlorination, sulfonamidation, and their antienteroviral activity has been evaluated. Two compounds, namely, ethyl 4-((1-(cyclobutanecarbonyl)indoline)-5-sulfonamido)benzoate and ethyl 4-((1-benzoylindoline)-5-sulfonamido)benzoate exhibited a medium level of activity against coxsackievirus B3 (Nancy strain) in vitro. Their antiviral potential is exerted upon prophylactic application when added to cell culture before infection with the virus. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Development of novel chalcone derivatives as multifunctional agents for the treatment of Alzheimer ’s disease
AbstractTo develop multifunctional agents for the treatment of Alzheimer ’s disease (AD), a series of novel chalcone derivatives was developed as the multitarget-directed ligands. Their MAOs inhibitory activities, anti-inflammation properties and neuroprotective effects were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good sele ctive MAO-B inhibitory activity. Among them, compound3i exhibited the best MAO-B inhibitory potency with IC50 values of 0.092 μM, and the molecular docking provide possible mechanism for its high MAO-B inhibitory potency. Compound3i also significantly ...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Exploring the latest breakthroughs in rhodesain inhibitors for African trypanosomiasis
AbstractHuman African Trypanosomiasis is a serious public health concern, and new chemical therapeutic agents need to be developed to combat this disease. Rhodesain (RhD) inhibitors have shown promising results in medicinal chemistry, specifically againstTrypanosoma brucei. These inhibitors target the cysteine protease RhD, which is essential for the survival ofT. brucei. However, as the pharmaceutical industry lacks interest in these inhibitors, the development of drugs based on them is challenging. In this review, we showed the impact of RhD inhibitors on medicinal chemistry in the past 10 years (2013 –2022), particula...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Preliminary structure −activity relationships analysis on N-(3,5-dichlorophenyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-amine, a disruptor of mycobacterial energetics
AbstractThe increasing emergence of drug-resistance among mycobacteria represents a serious global health threat, requiring novel and effective therapeutic strategies. The lack of innovation in the drug discovery approach and/or in the combination of the therapeutic cocktail makes inevitable the onset of resistance also for the newly marketed drugs such as bedaquiline and delamanid. Therefore, different therapeutic tools are urgently required. Adjuvant therapies (AT), that is those approaches aimed at boosting the existing treatment, rather than replacing it with another, have gained increasing consideration in the antibac...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Identification of novel benzoyl hydrazine derivatives as activators of neddylation pathway to inhibit the tumor progression in vitro
AbstractNeddylation modification is frequently overexpressed in many types of human tumors. As a result, targeting neddylation pathway has been identified as viable anticancer therapeutic strategy. The NEDD8-activating enzyme (NAE) serves as a crucial role in a variety of cellular functions. Here, a new library of piperidine analogs was developed, produced and assessed for antiproliferative efficacy against A549, MGC-803, MCF-7KYSE-30 cell lines. The cell-based mechanistic studies showed thatIIb-10 bearing the benzoyl hydrazine motif can selectively inhibit the Neddylation modification of Cullin1 and Cullin3 by inhibiting ...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Insights on synthetic strategies and structure-activity relationship of donepezil and its derivatives
AbstractThis comprehensive review focuses on the synthesis and derivatives of donepezil, a pivotal Alzheimer ’s disease (AD) medication introduced in 1997. As a selective acetylcholinesterase inhibitor with 100% oral bioavailability and a 70-h half-life, donepezil’s success in neurodegenerative disorder management has spurred extensive research into its synthesis and structural modifications. The revie w examines diverse synthetic approaches, evaluating their efficiency, cost, toxicity, and scalability. Methods range from traditional hazardous chemicals to eco-friendly strategies. Structural modifications and their imp...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Targeting disease with benzoxazoles: a comprehensive review of recent developments
AbstractBenzoxazole is an attractive scaffold in medicinal chemistry due to its diverse biological applications. From 2016 to 2023, a plethora of benzoxazole derivatives have been synthesized and evaluated for their pharmacological activities but a review on this topic was found lacking. This review thus aims to fill the gap and discusses the pharmacological activities of the synthesized derivatives, emphasizing their interactions with key biological targets implicated in diseases such as cancer, diabetes, pain, inflammation, and cardiovascular disorders. Relevant works were selected mainly from databases such as PubMed an...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
Synthesis, characterization, and anticancer activity of syringaldehyde-derived chalcones against female cancers
AbstractA series of novel chalcone analogs derived from syringaldehyde have been synthesized through acid or base-catalyzed aldol condensation. The anticancer activity of the newly synthesized compounds was assessed against a range of women-specific cancer cell lines, including A2780 (ovarian cancer), HeLa and C33a (cervical cancer), and MDA-MB-453, MDA-MB-231 and MCF-7 (breast cancer). The majority of these compounds demonstrated remarkable cytotoxicity against the tested cancer cells. Compound2a displayed the most promising anti-proliferation activity against the selected female cancer cells, while also exhibiting the we...
Source: Medicinal Chemistry Research - March 1, 2024 Category: Chemistry Source Type: research
