The rising prevalence of multidrug-resistant pathogens and the global burden of cancer necessitate the development of new therapeutic agents using sustainable, innovative approaches. Pyrimidine derivatives have attracted considerable attention due to their diverse biological activities, including antimicrobial and anticancer properties. Despite numerous reports on their synthesis, a clear gap remains in the literature regarding green synthesis protocols that combine eco-friendly reaction conditions with comprehensive biological and computational evaluations. In this work, we report a sustainable synthesis of these compounds using both conventional and microwave-assisted methods. Furthermore, we provide detailed characterization and in vitro assessments of biological activity. Compounds 7c, 8c, and 10a showed promising results, while extensive computational studies (DFT, molecular docking, and MD simulations) were conducted to elucidate the structure–activity relationships. This integrated approach not only deepens understanding of the pharmacological potential of these compounds but also aligns with the principles of green chemistry, offering a promising pathway for future drug discovery.
To explore more potential fungicides with new scaffolds, 10 norbornene derivatives containing thiourea group were designed, synthesized and assayed for inhibitory activity against three plant pathogenic fungi. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, norbornene derivatives 3g presented excellent in vitro antifungal activity against Botryosphaeria dothidea (EC50 = 9.51 mg/L), which was approached to chlorthalonil. In vivo antifungal assay indicated norbornene derivatives 3g displayed excellent protective and curative effects on apple fruits infected by B. dothidea. The preliminary mechanism study displayed that norbornene derivatives 3g could damage the surface morphology. In addition, the phytotoxicity test revealed norbornene derivatives 3g showed safety on seeds of mung bean. The bioassay results and mechanism investigation demonstrated that this class of norbornene derivatives containing thiourea group could be promising fungicide for further development.
In face of large-scale plant diseases, the control of chemical pesticides remained a fast, economical and effective method. The search for novel bioactive pesticide has long been a priority in crop protection for solve the plant pathogen resistance. Natural products and their derivatives have been the major sources of the discovery of novel fungicides. Succinate dehydrogenase inhibitors (SDHIs) fungicides are the third largest category of fungicides. Meanwhile, the resistance of SDHIs with plant pathogen had been an urgent problem. It was an effective way to delay the resistance problem by the creation of fungicides from natural product. Considering these issues, here we have reviewed the published articles on the SDHIs fungicides during past five years (2020–2024) based on three kinds of natural product scaffolds.
Chiral γ-nitroketone-derived pyrrolidine N-oxide (III) exhibited potent in vitro anti-tumor activity against three cancer cell lines: human breast carcinoma (MDA-MB-231), human colorectal carcinoma (SW-480), and murine colorectal carcinoma (CT-26), with IC50 values of 8.81 ± 0.12 μM, 9.07 ± 0.31 μM, and 5.68 ± 0.10 μM, respectively. Informed by the findings, a series of quinoline-derived chiral γ-nitroketones were synthesized via an efficient organocatalytic asymmetric strategy, achieving excellent yields (up to 99 %) and enantioselectivities (up to 99 % ee). This synthetic strategy involves enantioselective Michael additions between nitroalkanes and 2-enoylquinolines, catalyzed by a bifunctional squaramide under solvent-free conditions.
A novel series of triazolothiadiazines has been successfully synthesized with high efficiency through Knoevenagel condensation, utilizing thiocarbamoyl dihydrazine as the starting material. The structures of these compounds were characterized through 1 H-NMR, 13 C-NMR, high-resolution mass spectrometry. The MTT assay was utilized to evaluate the in vitro cytotoxicity of the synthesized compounds against four human cancer cell lines including SW620, A549, Hela, and MCF-7. Among the tested compounds, (Z)-3-methyl-6-phenyl-7-(3-(trifluoromethyl)benzylidene)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine exhibited notably potent antiproliferative activity against all four human cancer cell lines.
The synthesis of 1,2,3-triazoles, which are acting as promising pharmacophores with strong biological activity, is the focus of our work. Three obscure streaks of hybrid molecules with a 1,2,3-triazole nucleus have been synthesized by us. Compounds are synthesized in two steps: first, an azide is formed from its amine equivalent, next 1,2,3-triazole ring is formed utilizing azide-alkyne click chemistry. The obtained yields range from fair to good. After testing, it is discovered that the compounds 1c, 2a, 2c, 3a have good antibacterial properties and compounds 2b, 3a have promising antifungal properties. The compounds are found to be soluble in ethanol, ethyl acetate. The primary difficulty we encountered was with cyclopropane as the reaction needed to be carried out under reflux at 100°C, and its boiling point is 51°C.
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme associated with tumor immune evasion, making it a promising target for cancer therapy. This study aimed to identify novel holo-IDO1 inhibitors with distinct structural scaffolds. A series of theophylline derivatives containing 1,2,3-triazole groups were designed and synthesized through the condensation of theophylline acetic acid and 4-aminophenylacetylene. Among the synthesized compounds, 3c and 3e exhibited the most potent inhibitory effects in IDO1 enzymatic activity assays. Molecular docking and affinity prediction analyses provided insights into the binding affinities and mechanisms of action of the lead compounds. Our findings suggest that theophylline derivatives are promising holo-IDO1 inhibitors, warranting further development for potential therapeutic applications.
This review article summarizes the role of heterocyclic compounds as anticancer drugs used against various human cancers, including doxorubicin, cisplatin, paclitaxel, and resveratrol, which are among the most effective therapeutic agents. Chemotherapy, a treatment modality, exerts its effects on tumor cell DNA and often involves the use of low-molecular-weight medicines to selectively target and destroy cancer cells. However, systemic chemotherapy is associated with several side effects, such as nausea, vomiting, myelosuppression, and cardiotoxicity. Cancer remains one of the most prevalent and lethal diseases, characterized by uncontrolled cell division and abnormal cell growth driven by multiple genetic mutations. The etiopathogenesis of cancer is complex, but significant advancements have been made in treatment, particularly with the discovery of anticancer drugs, including cytotoxic chemotherapy, hormonal agents, and targeted therapies. Anticancer drugs are widely employed for the treatment of various cancers, such as breast, cervical, uterine, and kidney cancers. These drugs are classified into several categories, including alkylating agents, antimetabolites, antibiotics, and topoisomerase inhibitors. Among these, numerous heterocyclic compounds have shown promising anticancer properties. The goal of this review is to compile information on heterocyclic compounds used as anticancer drugs, highlighting their positive effects and therapeutic targets in cancer treatment and chemoprevention.
A novel series of meta-diamide compounds incorporating a pyrazole moiety (2a-2v) were designed and synthesized based on cyproflanilide. Their structures were validated through 1H NMR, 13C NMR, and HRMS analyses. These compounds were evaluated for their insecticidal activity against Plutella xylostella, Mythimna separate, Tetranychus cinnabarinus, and Nilaparvata lugens. Most of the title compounds exhibited good activity against N. lugens at 400 mg/L. Compound 2k demonstrated potential for further optimization as an insecticidal lead, thereby extending the application of meta-diamide compounds in the field of sucking mouthparts.
A novel water-soluble substituted pyridine dicarboxylate containing a quaternary ammonium ion with potential applications in fluorescence cell imaging was synthesized and characterized. Remarkably, this compound exhibited water solubility in the absence of additional solubilizers, enabling direct dissolution in phosphate-buffered saline for cell studies. No obvious cytotoxicity was observed in 4T1 cells (mouse breast cancer cells) within the concentration range of 0.2-25 mu mol L-1, with a cell survival rate above 89%. Furthermore, the compound exhibited a maximum two-photon absorption cross-section of 86 GM at an excitation wavelength of 780 nm, demonstrating high cell permeability, effective distribution in the cytoplasm, and preferential targeting of organelles. Single- and two-photon fluorescence imaging of cells revealed a distinctive blue emission and strong bright green emission, respectively. The newly synthesized substituted pyridine dicarboxylate exhibited low cytotoxicity and strong fluorescence imaging properties, demonstrating its potential in cell imaging applications.
Research on gold catalysis has flourished over the last 20 years, and gold catalysts are now acknowledged as the “best choice” for a range of organic transformations. Gold complexes have emerged as promising candidates for this use in recent years because of their high reactivity, which enables them to induce a broad range of transformations under mild conditions. Extensive demonstrations have showcased the extraordinary efficiency of synthesizing complex organic compounds from the basic starting components. In addition to its traditional applications in catalysis, gold catalysis has expanded to include the total synthesis of natural compounds, which is a complex and demanding undertaking. The class of molecules known as carbo- and heterocycles, which is arguably the most important, has a significant impact on the synthesis of agrochemicals and pharmaceuticals among the numerous additional products made possible by the novel procedures pioneered. The main topic of this review is how to use Au salts in homogeneous catalysis to create cyclization processes for small heterocyclic and carbocyclic systems. This study gives an overview of most of the books and articles written after 2013 that discuss making three- and four-membered carbo- and heterocyclic rings with gold as a catalyst. We have made every effort to include all outstanding reports on this subject; nonetheless, we apologize for any omissions.
As part of our ongoing antileishmanial structure–activity relationship study, a structural simplification of the 3‐nitroimidazo[1,2‐a]pyridine ring to a 5-nitroimidazole moiety was conducted. A series of novel 2,4-disubsituted 5-nitroimidazole derivatives, including the 5-nitroimidazole analog of Hit A and the 4-phenylsulfonylmethyl analog of fexinidazole, were obtained by using the vicarious nucleophilic substitution of hydrogen (VNS) reaction, to substitute position 4, and by using the tetrakis(dimethylamino)ethylene methodology to modulate position 2. The molecular structures of eight novel 5-nitroimidazoles were characterized by 1H NMR, 13C NMR, LC/MS, and HRMS. The in vitro antileishmanial activity of these compounds was evaluated against the promastigote form of Leishmania infantum and their influence on cell viability was assessed on the human hepatocyte HepG2 cell line. The 4-phenylsulfonylmethyl analog of fexinidazole showed the best selectivity index of the series, displaying good activity against both the promastigote form of L. infantum (EC50 = 0.8 µM, SI > 78.1) and the promastigote form of Leishmania donovani (EC50 = 4.6 µM, SI > 13.6), and exhibiting low cytotoxicity on the HepG2 cell line (CC50 > 62.5 µM).
Triazoles act as important pharmacophores in showing biological activity such as antibacterial, antifungal, antitumour/anticancer, anti-inflammatory activities. Literature review suggests that triazoles have been maximally used in carrying research related activities in reference to biological evaluation as compared to other nitrogen containing five membered heterocycles like tetrazoles, pentazoles, pyrazoles, and imidazoles. The first compound of this class was discovered by Janseen Group in 1960s. The microbes act counteractively towards antibiotics which in turn challenge the efficacy of the drugs and thus create room for the progression of more potent avant-garde drugs. Thus, the synthesis of hybrid molecules has been accelerated from last two decades as the hybrids possess more potency, vigour, and adequacy than its constituting pharmacophores. So, this review represents a condensed report of the research carried out in relation to synthetical procedures and assessment of the antibacterial and antifungal activity of triazoles.
Research on gold catalysis has flourished over the last 20 years, and gold catalysts are now acknowledged as the "best choice" for a range of organic transformations. Gold complexes have emerged as promising candidates for this use in recent years because of their high reactivity, which enables them to induce a broad range of transformations under mild conditions. Extensive demonstrations have showcased the extraordinary efficiency of synthesizing complex organic compounds from the basic starting components. In addition to its traditional applications in catalysis, gold catalysis has expanded to include the total synthesis of natural compounds, which is a complex and demanding undertaking. The class of molecules known as carbo- and heterocycles, which is arguably the most important, has a significant impact on the synthesis of agrochemicals and pharmaceuticals among the numerous additional products made possible by the novel procedures pioneered. The main topic of this review is how to use Au salts in homogeneous catalysis to create cyclization processes for small heterocyclic and carbocyclic systems. This study gives an overview of most of the books and articles written after 2013 that discuss making three- and four-membered carbo- and heterocyclic rings with gold as a catalyst. We have made every effort to include all outstanding reports on this subject; nonetheless, we apologize for any omissions.
Imidazoles have a unique position in heterocyclic chemistry as these constitute the basic framework of several bio-molecules. Thus, increasing research is being carried out on the synthesis of imidazoles and their derivatives, mainly because of the application of imidazoles in pharmaceutical and medicinal research. Keeping sustainability in mind, researchers are developing synthetic pathways for the synthesis of imidazoles and their derivatives by employing techniques involving green tools, thus leading to sustainable pathways. In this review, we aim to compile such synthetic methodologies involving green tools for the synthesis of imidazoles. The review will cover the synthetic reactions that involve green tools such as microwave irradiation, ultrasound irradiation, and ball milling. We aim to highlight the scope and relevance of such green tools in today’s synthetic research. Through this review, we wish to contribute towards the synthesis of imidazoles that serve as a useful class of heterocyclic compounds involved in the development of pharmaceutically active molecules. We sincerely hope that this review will serve as a relevant guide for future sustainable research in the synthesis of imidazoles and their derivatives.
Since many of the U.S. Food and Drug Administration (FDA)-approved medications contain oxygen-containing heterocyclic molecules, they have been discovered to be quite important. Moreover, over the past 10 years, the field of reusable nanocatalysts has expanded quickly. Therefore, the development of nanotechnology has led to a wide range of applications for nanocatalysis in the synthesis of heterocyclic molecules. The domains of organic chemistry and pharmaceuticals have recently shown a great deal of interest in nanocatalyzed organic processes. Such nanocatalysts enable non-toxic, simpler, environmentally friendly, and more affordable synthetic processes that give only the most desirable compounds in higher quantities and provide simple catalyst separation. As a result of their efficient methods for separating catalysts and products, nanocatalysts were chosen over other catalysts for the synthesis of heterocyclic compounds. This review emphasized the preparation of nanocatalysts, synthetic approaches, and recycling studies of highly excited catalytic systems employed for the synthesis of oxygen-containing heterocyclic compounds.
Imidazole and its derivatives possess remarkable versatility, finding applications in medicine, synthetic chemistry, and industry. This review explores the latest advancements observed over the last few years (2018–2022), focusing on diverse multicomponent reactions conducted under different conditions. It highlights the role of catalysts and diverse conditions, optimizing synthetic efficiency. The review offers concise insights into emerging trends, making it a valuable resource for researchers and practitioners seeking greener and more efficient imidazole synthesis.
Lung cancer shows a high rate of incidence and mortality. This study aimed to investigate the influence of octreotide (OCT) on lipopolysaccharide (LPS)-induced apoptosis and metabolome expression in A549 cells. After A549 cells were treated by LPS or co-cultured with LPS and OCT, cell apoptosis was tested by flow cytometry, and gas chromatography-mass spectrometer (GC/MS) and high-performance liquid chromatography-mass spectrometer (LC/MS) were subjected to determine the differently expressed metabolites, and the interaction network was constructed. Results found that OCT promoted the apoptosis of A549 cells and significantly affected LPS-regulated cell apoptosis. Following the further investigation by orthogonal partial least squares discriminant analysis (OPLS-DA), the metabolites with different expression levels were obtained, and most of which belong to amino acids, phospholipids, organic acid, and saccharides. Fourteen components with the role of the marker metabolites included serotonin, indole, threonine, serine, glucose, phenylalanine, lactose, fumarate, 4-hydroxyphenyllactate, aspartate, asparagine, putrescine, proline, and succinate. It is indicated that OCT promotes apoptosis through five metabolism pathways and 14 key metabolism elements in A549 cells.
A series of novel quinazoline derivatives bearing sulfonamide moiety was designed and synthesized, and their structure were characterized by H-1 NMR, C-13 NMR, and HRMS techniques. Among them, the structure of compound E1 was further confirmed through X-ray single-crystal diffraction analyses. Their anti-Tobacco mosaic virus (TMV) activities were evaluated through half-leaf method. The bioassay results showed that E8 and E19 possess excellent inhibitory activity towards TMV. The EC50 of curative activities, protective activities, and inactivating activities of E8 and E19 are 132.1, 152.8, 57.4 mg/L and 278.0, 165.3, 94.5 mg/L, respectively, which are far superior than Ribavirin (318.2, 201.5, 128.6 mg/L, respectively).
The present work deals with the synthesis of 2-cyano-N'-(3-(2-(2-cyanoacetyl) hydrazinyl) cyclohex-2-en-1-ylidene) acetohydrazide 3 that used as a key precursor in the manufacture of new heterocyclic derivatives, such as pyrazole, pyrane, pyridine and pyrole incorporating cyclohexene moiety via its reaction with a variety of nucleophilic and electrophilic reagents. The newly synthesized compounds were characterized by their elemental analyses (IR, 1 H-NMR, 13 C-NMR and Mass spectra) and assessed for their anti-microbial activity.
