Vol 23, No 11 (2023)

Background: Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. Inhibition of isoforms IX and XII has induced potent anticancer effects.

Objective: A series of indole-3-sulfonamide-heteroaryl hybrid (6a-y) was synthesized and screened for the inhibition of human (h) hCA isoforms I, II, IX, and XII.

Methods: The synthesis of target compounds (6a-y) was carried out in multistep starting from 5-nitro indole as starting material by using classical reported reaction conditions. The steps involved are N-Alkylation Chlorosulfonation, amination, reduction, and finally amidation reaction.

Results: Amongst all the compounds (6a-y) synthesized and screened, 6l was found to be active against all the screened hCA isoforms, with Ki ranging 8.03 µM, 4.15 µM, 7.09 µM, and 4.06 µM respectively. On the other hand, 6i, 6j, 6q, 6s, and 6t were highly selective against tumor-associated hCA IX, and 6u was selective against both hCA II and hCA IX with moderate inhibitory activities under the range of 100 µM. These compounds showed good activity against the tumor-associated hCA IX and might be developed as future drug leads for anticancer drug discovery.

Conclusion: These compounds may be useful as starting points for the design and development of more selective and potent hCA IX and XII inhibitors.

CSCs (Cancer stem cells) are a subpopulation of transformed cells residing within the tumour that possesses properties of stem cells, like self-renewal and differentiation. Different signalling pathways, epigenetic changes, and interaction with a tumour microenvironment are found to be involved in the maintenance of stemness of CSCs and contribute to chemoresistance. Hence, it is difficult to prevent and control progression completely without considering CSCs as a crucial target. Some phytochemicals target different pathways and gene expression and modulate CSC markers to suppress the stemness properties of cancer cells. Thus, phytochemicals potentially impact CSCs which may be applied in chemo-prevention. This comprehensive review discusses some studied phytochemicals that suppress stemness characters in various cancer types both in vitro and in vivo animal models. However, the chemo-prevention ability of phytochemicals needs to be validated in further subsequent stages of clinical trials.

Chalcones are members of the flavonoid family and act as intermediates in the biosynthesis of flavonoids, which are widespread in plants. Meanwhile, chalcones are important precursors for synthetic manipulations and act as mediators in the synthesis of useful therapeutic compounds, which have demonstrated a wide range of biological activities. Numerous studies have reported the synthesis and medicinal significance of chalcone derivatives. Cancer is one of the major causes of death worldwide. Although various therapies have been proposed for diverse types of cancer, their associated limitations and side effects urged researchers to develop more safe, potent and selective anticancer agents. Based on the literature review, the presence of chalcone derivatives as the main component, a substituent, or a side-chain in different biologically active compounds could serve as a reliable platform for synthetic organic chemists to synthesize new compounds bearing this moiety, owing to their similar or superior activities compared to those of the standards. The diversity of the chalcone family also lends itself to broad-spectrum biological applications in oncology. This review, therefore, sheds light on the latest structure and the anticancer potency of different synthetics (bearing other anticancer pharmacophores based on simple, functional groups, and dimer chalcone derivatives) and natural chalcone hybrids. It is confirmed that the information compiled in this review article, many chalcone hybrids have been found with promising anticancer activities. Therefore, this review may be convenient for designing novel chalcone molecules with enhanced medicinal properties according to the structure of the compounds.

Background: The diagnosis of uterine dysfunction (endometrial hyperplasia) is on the rise. The available treatment is quite expensive and associated with some side effects. The therapeutic potential of natural products is now being explored, as they are easily available with little or no side effects. Drymaraia cordata is folklorically utilized in the treatment of diverse ailments including uterine fibroids

Objectives: This study aims to investigate the potential therapeutic effect of chloroform fraction of methanol extract of Drymaria cordata (CFDC) in estradiol benzoate (EB)-induced endometrial hyperplasia.

Methods: Thirty-six rats were randomly divided equally into six groups. These included control group, CFDC: (100 mg/kg), CFDC: (200 mg/kg), EB: (2 mg/kg), EB + CFDC (100 mg/kg), and EB + CFDC (200 mg/kg). Endometrial hyperplasia (EH) was induced by intraperitoneal injection of EB. The levels of estrogen (E2), progesterone (PG), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Malondialdehyde (MDA), Superoxide dismutase (SOD), and Glutathione peroxidase (GSH-Px) activities were determined using ELISA technique. The uterine histological assessment and immunohistochemical expression levels of estrogen receptor, Ki-67, cytochrome c, and caspase 3 were carried out.

Results: EH was severely expressed in the uterine section of EB-treated rats. However, CFDC administration improved the pathological features of the animal model. The sex hormones levels were increased in the EB-treated group, which were significantly reduced by CFDC. The antioxidant indices were also restored by CFDC. Immunoexpression levels of ERα and Ki-67 were downregulated while cytochrome c and caspase 3 were upregulated by CFDC.

Conclusion: This study suggests that CFDC contains phytochemicals that can protect against EB-induced EH via modulation of hormonal signaling, apoptotic machinery, and oxidative indices.

Background: Surgical resection and chemotherapy are the primary treatment options for cervical cancer; however, efficacy of chemotherapy drugs is limited by drug resistance. There is an urgent need to find new compounds. Gambogic acid lysinate (GAL), a new compound made from gambogic acid and lysine, has good anti-tumor activity, however, the effect of GAL on cervical cancer remains undetermined.

Objective: The present study sought to explore the anti-tumor activity of GAL in SiHa cells.

Methods: Cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, and Western blotting was employed to explore the mechanism of GAL. Additionally, the in vivo anti-tumor activity of GAL was studied through a xenograft tumor model in nude mice.

Results: GAL inhibited the proliferation of both SiHa cells (IC50 was 0.83 µmol/l and 0.77 µmol/l respectively for 48 h and 72 h) and HeLa cells (IC50 did not reach). In SiHa cells, GAL (1 and 2 µmol/l) inhibited cell proliferation and 2 µmol/l GAL could also induce cell apoptosis and decrease the number of S phase. Both 1 and 2 µmol/l GAL inhibited SiHa cells invasion and increased the number of G0/G1 phase. The results of Western blot assay demonstrated that P53 and P21 were involved in SiHa cells S phase arrest and BCL-2 and BAX were involved in SiHa cells apoptosis. In vivo study showed that the growth of SiHa cell xenograft tumors was inhibited via cell apoptosis induced by GAL (2.5 mg/kg body weight), however, GAL (2.5 mg/kg body weight) had no significant effect on weight gain of mice.

Conclusion: GAL induced SiHa cells apoptosis by BCL-2 and BAX pathway and SiHa cells S phase arrest by P53 and P21 pathway in vitro and inhibited the growth of SiHa cell xenograft tumors.

Background: The indole backbone is encountered in a class of N-heterocyclic compounds with physiological and pharmacological effects such as anti-cancer, anti-diabetic, and anti-HIV. These compounds are becoming increasingly popular in organic, medicinal, and pharmaceutical research. Nitrogen compounds' hydrogen bonding, dipole- dipole interactions, hydrophobic effects, Van der Waals forces, and stacking interactions have increased their relevance in pharmaceutical chemistry due to their improved solubility. Indole derivatives, such as carbothioamide, oxadiazole, and triazole, have been reported to act as anti-cancer drugs due to their ability to disrupt the mitotic spindle and prevent human cancer cell proliferation, expansion, and invasion.

Objectives: To synthesize new 5-bromoindole-2-carboxylic acid derivatives that function as EGFR tyrosine kinase inhibitors as deduced through molecular docking studies.

Methods: Different derivatives of indole (carbothioamide, oxadiazole, tetrahydro pyridazine-3,6-dione, and triazole) were synthesized and evaluated through different chemical, spectroscopic methods (IR, 1HNMR, 13CNMR, and MS) and assessed in silico and in vitro for their antiproliferative activities against A549, HepG2, and MCF-7 cancer cell lines.

Results: According to molecular docking analyses, compounds 3a, 3b, 3f, and 7 exhibited the strongest EGFR tyrosine kinase domain binding energies. In comparison to erlotinib, which displayed some hepatotoxicity, all of the evaluated ligands displayed good in silico absorption levels, did not appear to be cytochrome P450 inhibitors, and were not hepatotoxic. The new indole derivatives were found to decrease cell growth of three different types of human cancer cell lines (HepG2, A549, and MCF-7), with compound 3a being the most powerful while still being cancer-specific. Cell cycle arrest and the activation of apoptosis were the results of compound 3a's inhibition of EGFR tyrosine kinase activity.

Conclusion: The novel indole derivatives, compound 3a in particular, are promising anti-cancer agents which inhibit cell proliferation by inhibiting EGFR tyrosine kinase activity.

An article was published in the journal \"Anti-Cancer Agents in Medicinal Chemistry\", Volume 7, No. 01, 2007, pp: 55-73 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/3359