Design, synthesis and biological evaluation of novel pyrazole-based compounds as potential chemotherapeutic agents.

Design and synthesis of pyrazole-based chemotherapeutic agents. A series of novel diphenyl pyrazole-chalcone derivatives were synthesized and assessed for their cytotoxic activities against 14 cancer cell lines and their antimicrobial activities against MRSA and along with their safety using HSF normal cell line. Majority of the compounds showed moderate-to-significant anticancer activity with selective high percentage inhibition (>80%) against HNO-97 while being nontoxic toward normal cells.

Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors.

Activin receptor‑like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-β (TGF-β) family. (TGF-β) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target.

Design and synthesis of novel chloropyridazine hybrids as promising anticancer agents acting by apoptosis induction and PARP-1 inhibition through a molecular hybridization strategy.

Guided by the molecular hybridization principle, a novel series of 4-chloropyridazinoxyphenyl conjugates (3a-h, 4a-e, and 5) was designed and synthesized as proposed apoptotic inducers and PARP-1 inhibitors. The growth inhibition % of the designed hybrids was investigated in eleven cancer cell lines, where the anticancer activities were found to be in the following order: 4-chloropyridazinoxyphenyl-aromatic ketones hybrids (3a-h) > 4-chloropyridazinoxyphenyl-benzyloxyphenylethan-1-one hybrids (4a-e) > 4-chloropyridazinoxyphenyl-thiazolidine-2,4-dione hybrid (5). Further, the most sensitive three cancer cell lines (HNO97, FaDu, and MDA-MB-468) were selected to measure the IC values of the new hybrids.

Identification of novel ureido benzothiophenes as dual VEGFR-2/EGFR anticancer agents.

Presently, dual-targeting by a single small molecule stands out as a fruitful cancer-fighting strategy. Joining the global effort to fight cancer, a leading cause of death worldwide, we report in this study a novel set for benzothiophene-based aryl urea derivatives as potential anti-proliferative candidates endowed with dual VEGFR-2/EGFR inhibitory activities. The prepared ureido benzothiophenes 6a-r have been evaluated for their anticancer action on a panel of tumor cell lines, namely PanC-1, MCF-7, and HepG2 cells.

Identification of 3-(5-cyano-6-oxo-pyridin-2-yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity.

New 5-cyano-6-oxo-pyridine-based sulfonamides (6a-m and 8a-d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D.

Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer.

Hypoxia, a characteristic feature of solid tumors, develops as a result of excessive cell proliferation and rapid tumor growth exceeding the oxygen supply, and can result in angiogenesis activation, increased invasiveness, aggressiveness, and metastasis, leading to improved tumor survival and suppression of anticancer drug therapeutic impact. SLC-0111, a ureido benzenesulfonamide, is a selective human carbonic anhydrase (hCA) IX inhibitor in clinical trials for the treatment of hypoxic malignancies. Herein, we describe the design and synthesis of novel 6-arylpyridines 8a-l and 9a-d as structural analogues of SLC-0111, in the aim of exploring new selective inhibitors for the cancer-associated hCA IX isoform.

Towards discovery of novel scaffold with potent antiangiogenic activity; design, synthesis of pyridazine based compounds, impact of hinge interaction, and accessibility of their bioactive conformation on VEGFR-2 activities.

Pyridazine scaffolds are considered privileged structures pertaining to its novelty, chemical stability, and synthetic feasibility. In our quest towards the development of novel scaffolds for effective vascular endothelial growth 2 (VEGFR-2) inhibition with antiangiogenic activity, four novel series of pyridazines were designed and synthesised. Five of the synthesised compounds; namely ( exhibited potent VEGFR-2 inhibitory potency (>80%); with IC values ranging from low micromolar to nanomolar range; namely compounds with (1.

Development of novel synthesized phthalazinone-based PARP-1 inhibitors with apoptosis inducing mechanism in lung cancer.

Herein we report the synthesis of two series of 4-phenylphthalazin-1-ones 11a-i and 4- benzylphthalazin-1-ones 16a-h as anti-lung adenocarcinoma agents with potential inhibitory activity against PARP-1. All the newly synthesized phthalazinones were evaluated for their anti-proliferative activity against A549 lung carcinoma cell line. Phthalazinones 11c-i and 16b, c showed significant cytotoxic activity against A549 cells at different concentrations (0.

Pyridazine Based Scaffolds as Privileged Structures in anti-Cancer Therapy.

Pyridazines, their oxo derivatives; pyridazinone as well as fused bi- or tricyclic pyridazine containing scaffolds are key structural features of many biologically active compounds with diverse pharmacological applications, including cancer therapy. Since protein kinases play prominent role in tumor biology, the inhibition of its signaling pathway is considered an effective therapeutic option for the treatment of cancer.Based on the various advantages of pyridazines in drug design including modulation of the physico-chemical properties, improving ADME and toxicity profile as well as easy and diverse synthetic methods of access, makes them an invaluable tool for designing compounds as future drugs for targeted cancer treatment.