**1. Introduction**

The WHO has estimated that cancer will become the main cause of death over the upcoming years. Additionally, they have pointed to the dominance of breast cancer (according to the discovery of new cancer cases) in 2020, with more than 2.2 million new cases [1]. Correspondingly, cancer therapy, especially breast cancer, is a challenging area for medicinal chemists to develop treatments that inhibit the growth of cancer cells by

**Citation:** Elkaeed, E.B.; Yousef, R.G.; Elkady, H.; Gobaara, I.M.M.; Alsfouk, A.A.; Husein, D.Z.; Ibrahim, I.M.; Metwaly, A.M.; Eissa, I.H. The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1*H*-Indole Derivative: In Silico and In Vitro Approaches. *Processes* **2022**, *10*, 1391. https://doi.org/ 10.3390/pr10071391

Academic Editors: Iliyan Ivanov and Stanimir Manolov

Received: 4 July 2022 Accepted: 14 July 2022 Published: 17 July 2022

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interacting with specific molecular targets and subsequently killing them. Tumor growth and reproduction are associated with increased vascularity (angiogenesis) in cancer cells [2]. Accordingly, anti-angiogenesis mechanisms were considered as one of the potential ways to combat cancer [3]. The vascular endothelial growth factor (VEGF) pathway plays an important role in the incidence of angiogenesis [4]. The vascular endothelial growth factor receptors (VEGFRs) can be divided into three subtypes; VEGFR-1, VEGFR-2, and VEGFR-3. Among the most valuable targets in cancer management, VEGFR-2 is a transmembrane tyrosine kinase receptor that is correlated with cell proliferation, division, motility, adhesion, and angiogenesis [5]. Thus, blocking the VEGFR-2 signaling cascade inhibits cancer cell proliferation [6]. The fact that cancer cells express VEGFR-2 receptors more than normal cells has enabled scientists to create safe and selective drugs to combat angiogenesis in tumor cells without affecting normal cells [7].

Using computers, computational (in silico) chemistry is a scientific approach that applies theoretical and mathematical basics to address and solve chemical problems. Computational chemistry is widely used in the pharmaceutical industry for investigating interactions between potential drugs and biomolecular targets [8]. Our team have synthesized and examined various compounds that were designed as anti-VEGFR-2, belonging to different classes such as quinazoline [9–12], nicotinamides [13], benzoxazole [14], pyridine [15] dihydroquinolones [16], thiourea-azetidine [17,18], and quinoxaline-2 (1*H*)-one [19–23], in addition to thieno [2,3-*d*]pyrimidine [24]. Furthermore, our team utilized the basics of in silico chemistry as a successful tool in molecular design and docking [25,26], structural similarity [27], toxicity [28], ADMET [29], DFT [30,31], MD [32], and pharmacophore [33] investigation.

We herein employ our former experiences in both of in silico chemistry and drug discovery to introduce an effective and selective chemotherapeutic 1*H*-indole derivative focusing on VEGFR-2.
