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A series of isatin-based fused heterocycles were designed, synthesized, and evaluated for anticancer activity against four cancer cell lines: MCF-7, MDA-MB-231, A549, and HL-60. Among them, Q 3 and T 4 were found to be potent anticancer agents. Furthermore, two compounds Q 3 and T 4 were selected for epidermal growth factor receptor (EGFR) inhibitory activity. Two compounds Q 3 and T 4 were found to be most potent EGFR inhibitors with IC 50 of 0.22 ± 0.10 and 0.19 ± 0.07 μM. The EGFR inhibitory activity of standard drug erlotinib was 0.08 ± 0.02 μM. Structural Activity Relationship studies showed that electronegative atoms were necessary for EGFR inhibitory potential. Finally, molecular docking studies were carried out to check the binding pattern of synthesized derivatives with the adenosine triphosphate (ATP) binding site of EGFR and results revealed that compounds Q 3 (-9.2 kcal/mol) and T 4 (-8.9 kcal/mol) exhibited better binding affinity than reference drug erlotinib (-7.3 kcal/mol).

Cancer represents one of the world's biggest hazardous diseases. p53 is the uttermost researched tumour suppressor protein. It is commonly considered the "guardian of the genome," performing a critical function in genetic stability maintenance through controlling the cell cycle, programmed cell death, DNA repair, aging, and angiogenesis. The abnormalities in p53 lead to genetic instability and plays a significant role in carcinogenesis. The role of p53 in tumour suppression is emphasized in addition by the observation that primary silencing with this protein occurred in more than 50% of cancers. MDM2, p53, and the p53-MDM2 connections are well-known targets for the prevention and treatment of cancer. Moreover, in tumors with wild-type p53, their efficacy is decreased due to MDM2 enlargement or by the gradual decrease of MDM2 blocker ARF. As a result, improving p53 activity in cancerous cells provides a promising anticancer strategy. Various techniques are now being investigated, and addressing the p53-MDM2 interaction had also evolved as a potentially feasible strategy for contending with tumors. Both p53 and MDM2, interact via an autoregulation response signal: p53 activity induces MDM2 transcription, which in response interacts with p53's N-terminal transactivation domain, inhibiting its transcriptional activity. This article provides information on the current scenario of anti-tumor activities, with a particular emphasis on structure-activity relationship characteristics (SAR) against the p53-MDM2 to treat cancer. The primary purpose of this review is to cover recent advancements in the creation and testing of anticancer drugs that target the p53-MDM2 structure. This review contains different heterocyclic moieties which show significant results toward cancer. A mechanistic route is shown here, demonstrating both normal and malignant conditions via several stressed factors. Several compounds entered clinical trials as p53-MDM2 inhibitors for the treatment of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The severity and prevalence of cancer in modern time are a huge global health burden. Continuous efforts are being made toward the development of newer therapeutic candidates to treat and manage this ailment. The dihydropyrimidinone scaffold is one of the key nuclei that have been highly explored and investigated against cancer. It has the potential to combat the consequences of cancer by interacting with several biological targets. Tubulin polymerization inhibition is one such strategy to prevent the progression of cancer. In the presented work, we have synthesized a series of sixteen dihydropyrimidinone derivatives by following a rational drug design. The synthesized compounds have been characterized by 1 H NMR and 13 C NMR and were further evaluated for cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231), lung cancer cell lines (A549), and colon cancer cell lines (HCT-116). Compounds 5D and 5P were found most potent and revealed a better cytotoxic activity compared with the standard drug colchicine. Furthermore, the tubulin polymerization inhibition assay revealed that compound 5D showed better inhibition than colchicines, whereas compound 5P revealed an almost equal inhibition to that of colchicine. Furthermore, to investigate the possible mode of action and binding patterns, compounds 5P and 5D were subjected to molecular docking against tubulin (Protein Data Bank ID: ISA0). The results showed that compounds revealed significant interactions and were well occupied inside the cavity of tubulin. The compounds 5D and 5P may serve as new leads in drug development against cancer.

Background: Renal cell carcinoma (RCC) is a diverse collection of malignancies with varying histological characteristics, molecular changes, prognosis, and therapeutic response. Tivozanib was first approved in March 2021 by USFDA with the brand name Fotivda. Tivozanib hydrochloride monohydrate is an oral medication that is used to treat relapsed or refractory renal cell carcinoma., Objective: In this review, we explain renal cell carcinoma and its different types of treatment by the anti-renal carcinoma drugs., Methods: A comprehensive literature search was conducted in the relevant databases, like ScienceDirect, PubMed, ResearchGate, and Google Scholar, to identify the studies., Conclusion: Tivozanib is an oral VEGFR-1, VEGFR-2, and VEGFR-3 tyrosine kinase inhibitor that is extremely selective and powerful. It has much less affinity for other receptor tyrosine kinases than multi-targeted TKIs now in clinical use. Because of its long half-life in circulation, it may be able to block VEGFRs more consistently. Doserelated controllable hypertension is its most commonly seen drug-related side event. Fatigue, hoarseness, and diarrhea, which are all common side effects, are not dose-related. Because of its target specificity, tivozanib can work well with other medications that have low side effects. Blocking both the VEGF and mTOR signaling pathways at the same time provides the benefit of synergistic antitumor efficacy while also preventing treatment resistance. Thus, overall we can say that the drug tivozanib is suitable for treatment in patients with renal cell carcinoma and can be investigated in multi-center clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC 50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC 50 values of 4.67 µM & 3.38 µM and 4.63 µM & 3.71 µM against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity (in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a, was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cancer is a multifactorial disease and its genesis and progression are extremely complex. The biggest problem in the anticancer drug development is acquiring of multidrug resistance and relapse. Classical chemotherapeutics directly target the DNA of the cell, while the contemporary anticancer drugs involve molecular-targeted therapy such as targeting the proteins possessing abnormal expression inside the cancer cells. Conventional strategies for the complete eradication of the cancer cells proved ineffective. Targeted chemotherapy was successful in certain malignancies however, the effectiveness has often been limited by drug resistance and side effects on normal tissues and cells. Since last few years, many promising drug targets have been identified for the effective treatment of cancer. The current review article describes some of these promising anticancer targets that include kinases, tubulin, cancer stem cells, monoclonal antibodies and vascular targeting agents. In addition, promising drug candidates under various phases of clinical trials are also described. Multi-acting drugs that simultaneously target different cancer cell signaling pathways may facilitate the process of effective anti-cancer drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

1,2,4-triazole is an important nucleus present in a large number of compounds. More than thirty-five compounds containing this nucleus are introduced into the market. 1,2,4-triazole nucleus is stable to metabolism and acts as an important pharmacophore by interacting at the active site of a receptor as hydrogen bond acceptor and as a donor. Due to its polar nature, the triazole nucleus can increase the solubility of the ligand and it can significantly improve the pharmacological profile of the drug. A large number of 1,2,4-triazole derivatives are reported to possess a wide range of bioactivities including anti-cancer activity. This review article describes the role of 1,2,4-triazole nucleus in different types of anti-cancer agents such as nucleoside based anti-cancer agents, kinase inhibitors, tubulin modulators, aromatase and steroid sulfatase inhibitors, methionine aminopeptidase inhibitors, tankyrase inhibitors and metal complex based anti-cancer agents. It is expected that the current review article will provide insight into various ligand-receptor interactions and help in the rational design and development of novel 1,2,4-triazole based anti-cancer drugs with improved selectivity for cancer cells.

Cancer is a growing problem that has not yet been fully harnessed. Frequent mutations make this a highly variable and challenging pathology. Interestingly, mitochondria have currently emerged as a new target for cancer therapy. A group of agents with anticancer activity, termed mitocans that encourage apoptosis through mitochondrial disruption is currently important in research. From conventional glycolytic inhibitors to recent radiolabeled compounds, mitochondrial‐targeted therapies have marked their presence in cancer. Several TCA cycle and OXPHOS inhibitors are being established for their possible anticancer properties. There are so many distinctive differences in mitochondrial structure and function between normal and cancer cells that offer the potential for the clinical use of mitochondria as targets for novel and site‐specific anticancer agents. Mitochondrial targeting can be made possible if the bioactive molecule is specifically and selectively delivered to the mitochondria of the correct cell type using cell‐specific ligands and mitochondriotropic molecules. [ABSTRACT FROM AUTHOR]