Advancements in Synthetic Strategies and Biological Effects of Ciprofloxacin Derivatives: A Review.

Ciprofloxacin is a widely used antibiotic in the fluoroquinolone class. It is widely acknowledged by various researchers worldwide, and it has been documented to have a broad range of other pharmacological activities, such as anticancer, antiviral, antimalarial activities, etc. Researchers have been exploring the synthesis of ciprofloxacin derivatives with enhanced biological activities or tailored capability to target specific pathogens. The various biological activities of some of the most potent and promising ciprofloxacin derivatives, as well as the synthetic strategies used to develop them, are thoroughly reviewed in this paper. Modification of ciprofloxacin via 4-oxo-3-carboxylic acid resulted in derivatives with reduced efficacy against bacterial strains. Hybrid molecules containing ciprofloxacin scaffolds displayed promising biological effects. The current review paper provides reported findings on the development of novel ciprofloxacin-based molecules with enhanced potency and intended therapeutic activities which will be of great interest to medicinal chemists.

Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties.

BACKGROUND: There is a critical need for the discovery of novel and effective antibacterial or anticancer molecules. OBJECTIVES: Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%. METHODS: Their molecular structures were successfully confirmed using different spectroscopic methods including 1H/13C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method. RESULT: Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 µg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC50 value of 43.64 g/mL. CONCLUSION: The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required.

Antifungal Activities of Natural Products and Their Hybrid Molecules.

The increasing cases of drug resistance and high toxicity associated with the currently used antifungal agents are a worldwide public health concern. There is an urgent need to develop new antifungal drugs with unique target mechanisms. Plant-based compounds, such as carvacrol, eugenol, coumarin, cinnamaldehyde, curcumin, thymol, etc., have been explored for the development of promising antifungal agents due to their diverse biological activities, lack of toxicity, and availability. However, researchers around the world are unable to fully utilize the potential of natural products due to limitations, such as their poor bioavailability and aqueous solubility. The development of hybrid molecules containing natural products is a promising synthetic approach to overcome these limitations and control microbes' capability to develop resistance. Based on the potential advantages of hybrid compounds containing natural products to improve antifungal activity, there have been different reported synthesized hybrid compounds. This paper reviews different literature to report the potential antifungal activities of hybrid compounds containing natural products.

Synthesis of Ester-Linked Ursolic Acid-Based Hybrid Compounds: Potential Antibacterial and Anticancer Agents.

The molecular hybridization of two or more drugs into a single molecule is an effective drug design approach to reduce pill burden and improve patient treatment adherence. Ursolic acid-based hybrid compounds were synthesized and characterized followed by molecular docking studies. In vitro studies against various bacterial strains and human cancer cells (MDA-MB-231, HeLa, and MCF-7) were performed. Compounds 14-19, 21, 34, 31, and 30 demonstrated significant antibacterial activities with MIC values of 15.625 µg/ml. Compounds 29 and 34 were more cytotoxic than ursolic acid, with IC50 values of 46.99 and 48.18 µg/ml. Compounds 29 and 34 in the docking studies presented favourable binding interactions and better docking energy against the Epidermal Growth Factor Receptor (EGFR) than the parent compound, ursolic acid. The findings revealed that the ursolic acid scaffold is a promising precursor for the development of molecules with promising anticancer and antimicrobial activities. However, more studies are needed to fully understand their mode of action.

Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds.

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery.

Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.

Synthesis, Antibacterial, and Cytotoxicity Evaluation of Oleanolic Acid-4-aminoquinoline Based Hybrid Compounds.

AIM: The study aims to prepare a class of oleanolic-based compounds. BACKGROUND: Conventional drugs used to treat infectious diseases suffer from limitations such as drug toxicity and drug resistance. The resistance of microbes to antimicrobial agents is a significant challenge in treating microbial infections. Combining two or more drugs with different modes of action to treat microbial infections results in a delay in developing drug resistance by the microbes. However, it is challenging to select the appropriate drugs for combination therapy due to the differences in stability and pharmacokinetic profile of the drugs. Therefore, developing hybrid compounds using the existing drugs is a promising approach to design effective antimicrobial agents. OBJECTIVES: To prepare oleanolic-based hybrid compounds followed by characterization, in vitro antibacterial and cytotoxicity evaluation. METHODS: Oleanolic acid-4-aminoquinoline-based hybrid compounds were synthesized via esterification and amidation. The compounds were characterized using FTIR, NMR, and UHPLC-HRMS. Oleanolic acid (OA) was isolated from the flower buds of Syzygium aromaticum (L.) Merr. & L.M.Perry, a species from Kingdom Plantae, order Mytales in the Myrtaceae family. Antibacterial activity was determined against selected strains of bacteria using the microdilution assay and cytotoxicity activity was assessed using the sulforhodamine B assay against selected cancer cell lines. RESULTS: The synthesized hybrid compounds exhibited antibacterial activity against the Gram-positive bacteria Enterococcus faecalis (ATCC13047), Bacillus subtilis (ATCC19659), Staphylococcus aureus as well as Gram-negative bacteria, Klebsiella oxytoca (ATCC8724), Escherischia coli (ATCC25922), and Proteus vulgaris (ATCC6380) with minimum inhibitory concentrations of 1.25 mg/mL compared to oleanolic acid (2.5 mg/mL). Compounds 13 and 14 displayed cytotoxicity in vitro against the cancer cell lines (MCF-7 and DU 145) compared to the oleanolic acid (IC50 ˃ 200 µM). CONCLUSION: Modification of C28 of OA enhanced its biological activity.

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update.

Ursolic acid is a pharmacologically active pentacyclic triterpenoid derived from medicinal plants, fruit, and vegetables. The pharmacological activities of ursolic acid have been extensively studied over the past few years and various reports have revealed that ursolic acid has multiple biological activities, which include anti-inflammatory, antioxidant, anti-cancer, etc. In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid. These structurally modified compounds display enhanced therapeutic effects when compared to ursolic acid. This present review summarizes various synthesized derivatives of ursolic acid with anti-cancer activity which were reported from 2015 to date.

Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers.

Cancer is a life-threatening disease and is the second leading cause of death around the world. The increasing threats of drug-resistant cancers indicate that there is an urgent need for the improvement or development of more effective anticancer agents. Curcumin, a phenolic compound originally derived from turmeric plant (Curcuma longa L. (Zingiberaceae family)) widely known as a spice and a coloring agent for food have been reported to possess notable anticancer activity by inhibiting the proliferation and metastasis, and enhancing cell cycle arrest or apoptosis in various cancer cells. In spite of all these benefits, the therapeutic application of curcumin in clinical medicine and its bioavailability are still limited due to its poor absorption and rapid metabolism. Structural modification of curcumin through the synthesis of curcumin-based derivatives is a potential approach to overcome the above limitations. Curcumin derivatives can overcome the disadvantages of curcumin while enhancing the overall efficacy and hindering drug resistance. This article reports a review of published curcumin derivatives and their enhanced anticancer activities.

Antiviral Activities of Oleanolic Acid and Its Analogues.

Viral diseases, such as human immune deficiency virus (HIV), influenza, hepatitis, and herpes, are the leading causes of human death in the world. The shortage of effective vaccines or therapeutics for the prevention and treatment of the numerous viral infections, and the great increase in the number of new drug-resistant viruses, indicate that there is a great need for the development of novel and potent antiviral drugs. Natural products are one of the most valuable sources for drug discovery. Most natural triterpenoids, such as oleanolic acid (OA), possess notable antiviral activity. Therefore, it is important to validate how plant isolates, such as OA and its analogues, can improve and produce potent drugs for the treatment of viral disease. This article reports a review of the analogues of oleanolic acid and their selected pathogenic antiviral activities, which include HIV, the influenza virus, hepatitis B and C viruses, and herpes viruses.