Search

The use of medicinal plants has gained renewed wide popularity in Africa, Asia, and most parts of the world because of the decreasing efficacy of synthetic drugs. Thus, natural products serve as a potent source of alternative remedy. Tetrapleura tetraptera is a medicinal plant with cultural and traditional significance in West Africa. In addition to the plant being commonly used as a spice in the preparation of traditional spicy food for postpartum care it is also widely used to constitute herbal concoctions and decoctions for treatment of diseases. This review aimed to provide an up-to-date information on the ethnomedicinal uses, pharmacological activities and phytoconstituents of T. tetraptera. Preclinical studies regarding the plant's toxicity profile were also reviewed. For this updated review, literature search was done on PubMed, Science Direct, Wiley, and Google Scholar databases using the relevant keywords. The review used a total of 106 papers that met the inclusion criteria from January 1989 - February 2022 and summarised the bioactivities that have been reported for the rich phytoconstituents of T. tetraptera studied using various chemical methods. Considering the huge report, the review focused on the antimicrobial and antiinflammatory activities of the plant extracts and isolated compounds. Aridan, aridanin and several bioactive compounds of T. tetraptera have shown pharmacological activities though their mechanisms of action are yet to be fully understood. This study also highlighted the influence of plant parts and extraction solvents on its biological activities. It also presented data on the toxicological profile of the plant extracts using different models. From cultural uses to modern pharmacological research the bioactive compounds of T. tetraptera have proved effective in infectious disease management. We hope that this paper provided a robust summary of the biological activities and toxicological profile of T. tetraptera, thus calling for more research into the pharmacological and pharmacokinetic activities of natural products to help combat the growing threat of drug resistance and provide guidelines for their ethnomedicinal uses.

The privileged structure binds to multiple receptors with high affinity, which is helpful to the development of new bioactive compounds. Indole is classified as a privileged structure, which may be one of the most important structural categories in drug discovery. As a special subset of indole compounds, 2-phenylindole seems to be one of most promising forerunners of drug development. In this paper, 106 articles were referenced to review the structural changes, biological activities and structure-activity relationship of compounds in recent 20 years, and classified them according to their pharmacological activities, from several aspects, including anticancer, antibacterial, anti-inflammatory, analgesic, antiviral, anti-parasite, the biological activities target to central nervous system, et al. It also points out the importance of artificial intelligence (AI) technology in discovery of new 2-phenylindole compounds in a broader prospect. This review will provide some ideas for researchers to develop new indole drugs.

In this paper, the synthesis, characterization and the leishmanicidal assessments of novel 8-(4-alkylpiperazinyl) caffeine derivatives have been described. These compounds are new caffeine hybrid molecules that are structurally composed of three compartments comprising caffeinyl, piperazinyl and N-alkyl/aryl residues. The synthesis was carried out through the bromination of caffeine via NBS to attain the 8-bromocaffeine (8-BC) followed by the S

Cysteine (Cys) and homocysteine (Hcy) are involved in maintaining homeostasis in the body and are relevant to various diseases. While the level of Cys and Hcy is much lower than GSH in the living system, which leads to a major challenge to selectively identify Cys/Hcy in the presence of large amounts of GSH. In this paper, an AIE fluorescent probe SQM-NBD was obtained by connecting NBD to the hydroxyl group of the fluorophore SQM-OH for selective detection of Cys/Hcy. Probe SQM-NBD had no fluorescence itself. But, under the disturbance of GSH, the fluorescence signal of probe SQM-NBD could be turned on by Cys/Hcy. The study of the response mechanism showed that probe SQM-NBD could release both SQM-OH and Cys/Hcy-NBD after reacting with Cys/Hcy. While Cys/Hcy continued to quench the fluorescence of SQM-OH through the combination of Michael addition and the ion rich environment, resulting in only the fluorescence signal of Cys/Hcy-NBD being observed. SQM-NBD appeared superior sensitivity to Cys/Hcy, with LOD of 54 nM and 72 nM, respectively. Significantly, probe SQM-NBD realized the application of fluorescence imaging of Cys/Hcy in HeLa cells, indicating that probe SQM-NBD has the potential for Cys/Hcy identification under physiological and pathological conditions.

Bardoxolone methyl (CDDO-Me) has exhibited positive therapeutic effects in clinical trials for diabetic nephropathy (DN), but serious safety risks in the heart exist because of the potential off-target response resulting from the highly active part of CDDO-Me. Herein, we reported a novel strategy to prepare Cathepsin B (CTSB) cleavable and improved water-soluble prodrugs of CDDO-Me. CTSB linkers connection to the highly active α-cyano-α, β-unsaturated ketone (CUK) part of CDDO-Me with the incorporation of polyethylene glycol (PEG) moieties, provided a series of prodrugs of CDDO-Me without CUK part exposure. Theoretically, these prodrugs shielding CUK part can be stably circulated and finally cleaved by CTSB in lysosomes to release CDDO-Me. In this paper, preliminary curative effects and safety of all prodrugs were determined. Wherein, prodrug 20 displayed relatively better activities than other prodrugs in inhibiting the release of NO from RAW264.7 cells, activating Keap1-Nrf2-ARE signaling pathway and inhibiting NF-κB signaling pathway, which were comparable to CDDO-Me. More importantly, prodrug 20 showed relatively lower human ether-a-go-go-related gene (hERG) inhibitory activity compared with CDDO-Me, which demonstrated prodrug 20 might be safer than CDDO-Me. In conclusion, the novel strategy of shielding CUK part with CTSB linkers provided a new idea for solving the limitations of CDDO-Me in clinical application.

Antibody-drug conjugates are gradually revolutionizing anticancer therapy. Payload is one of the most crucial components of ADC for high antitumor activity. However, there is no direct and real-time monitoring method for the intracellular release mechanism of the payload. Herein, we developed a theranostic payload that possessed dual functions of therapy and imaging. This payload consisted of the classic payload MMAE and the novel nitro-coumarin probe reported for the first time, which has the dual characteristics of electron transfer ability and the on-off fluorescence property. In this paper, the theranostic property of the novel payload has been preliminarily demonstrated. The fluorescence intensity of the payload in target cells greatly increased approximately 9 times in 120 min through the high content analysis, and the intracellular distribution of the payload could be directly monitored by a confocal microscope. In in vitro cytotoxicity assays, the payload showed broad-spectrum and high antitumor activity (0.09 nM to 1.2 nM), which was equivalent to the MMAE (0.06 nM to 1.1 nM). Moreover, the ADC loaded with L-233 maintained the theranositc property. In conclusion, our work developed a theranostic payload for the first time and provides a new direct and real-time monitoring method for intracellular studies of ADC payloads.

In this paper, we present a new donor-π bridge-acceptor type fluorescent probe, MIB, which bears two organelle-targeted groups, namely positively charged benzothiazole group for mitochondria and morpholine moiety for lysosomes. In aqueous solution, the nucleophilic addition of HSOsub3/subsup-/sup(as SOsub2/subdonor) to MIB blocked its long-range π-conjugation and ICT process and resulted in significant optical signal changes (blue-shifted UV absorbance and fluorescence), which enabled colorimetric and ratiometric fluorescent detection of HSOsub3/subsup-/supwith high selectivity and sensitivity (detection limit of 63.15 nM). MIB offers obvious advantages of good water-solubility, fast response time (within 1 min), unique dual lysosome/mitochondria targeting capability and has been applied to the sensing of endogenous and exogenous SOsub2/subin live cells through fluorescent imagingsub./subIn addition, the proposed probe has been utilized for the determination of bisulfite in real water, food and herbal medicine samples, showing good recovery (91.45 % - 109.3 %) and precision.

Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated from the roots and rhizomes of Valeriana jatamansi. Structurally, compounds 1-7 were the first examples of iridoids from V. jatamansi with unique α, β, γ, δ-unsaturated aldehyde fragment between C-11, C-4, C-5, C-9 and C-8; compound 8 was an unprecedented iridoid derivative with a methyl group (Me-10) at C-1, rather than C-8, and its plausible biogenetic pathway was proposed in this paper; compounds 22 and 23 were the first examples of Δ

The selective inhibition of inducible nitric oxide synthase (iNOS) has become an interesting goal for the treatment of diseases where the immune and inflammatory response of the organism is involved. Septic shock is one prominent example of this type of affections. In this paper, the design and synthesis of twelve substituted pyridinyl- imidamide derivatives is described, together with their biological evaluation as NOS inhibitors. The most potent and selective compound was N-(3-hydroxy-3-(pyridin-3-yl)propyl)acetimidamide 9a (IC50 = 4.6 µM, against iNOS). Pharmacological assays in aortic rat tissue, have confirmed its inhibitory activity on iNOS and the absence of undesired cardicovascular effects. In silico analysis of the most promising compounds (9a, 9b, 9e and 9g) have predicted good drug-likeness properties. Furthermore, they have shown an adequate cell viability. Docking studies carried out on 9a suggest a particular binding mode that involves the essential residue Glu377, and might explain its iNOS selectivity. From a chemical point of view, the article describes an unusual cyclization to obtain pyridinyl-pyrimidine derivatives with high yield., Centro de Supercomputación de la Universidad de Granada (CSIRC), Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV) y Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R y PID2020-116347RB-100), Biblioteca de la Universidad de Granada