Design, synthesis, in silico molecular docking, and ADMET studies of quinoxaline-isoxazole-piperazine conjugates as EGFR-targeting agents.

In this paper, we report the synthesis of quinoxaline-isoxazole-piperazine conjugates. The anticancer activity was evaluated against three human cancer cell lines, including MCF-7 (breast), HepG-2 (liver), and HCT-116 (colorectal). The outcomes of the tested compounds 5d, 5e, and 5f have shown more potent activity when compared to the standard drug erlotinib. In a cell survivability test (MCF-10A), three potent compounds (5d, 5e, and 5f) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 84 µM. Furthermore, the compounds 5d, 5e, and 5f were tested for tyrosine kinase EGFR inhibitory action using erlotinib as the reference drug and compound 5e was shown to be more potent in inhibiting the tyrosine kinase EGFR than sorafenib. In addition to this, molecular docking studies of compounds 5d, 5e, and 5f demonstrated that these compounds had more EGFR-binding interactions. The potent compounds 5d, 5e, and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 5d, 5e, and 5f followed Lipinski, Veber, Egan, and Muegge rules without any deviation.

Recent Developments on Phenstatins as Potent Antimitotic Agents.

BACKGROUND: Phenstatin and their derivatives display remarkable antiproliferative activity toward a wide variety of preclinical tumor models. Structural simplicity and excellent stability of phenstatins offer a stimulating premise for developing various derivatives with profound antimitotic activity and excellent cytotoxicity. OBJECTIVE: To do analysis of literature that phenstatins derivatives inhibit tubulin polymerization through their interaction at the colchicine binding site of microtubules and arrest the G2/M phase of the cell cycle. In addition, phenstatin derivatives are undergoing clinical evaluation as vascular targeting/disrupting agents and also exhibit direct antiangiogenic properties. METHODS: An organised well designed and appropriately managed search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/ exclusion criteria has been done for this article. CONCLUSION: In this review article, the synthesis and structure-activity relationships of phenstatin and a wide number of their reported analogues with modifications to ring A, ring B, and to the keto position are discussed in the perspective of medicinal chemistry with proper conclusion.

Development of combretastatins as potent tubulin polymerization inhibitors.

The combretastatins are isolated from South African tree combretum caffrum kuntze. The lead compound combretastatin A-4 has displayed remarkable cytotoxic effect in a wide variety of preclinical tumor models and inhibits tubulin polymerization by interacting at colchicine binding site of microtubule. However, the structural simplicity of C A-4 is favorable for synthesis of various derivatives projected to induce rapid and selective vascular shutdown in tumors. Majority of the molecules have shown excellent antiproliferative activity and are able to inhibit tubulin polymerization as well as possible mechanisms of action have been investigated. In this review article, the synthesis and structure-activity relationships of C A-4 and immense number of its synthetic derivatives with various modifications on the A, B-rings, bridge carbons and their anti mitotic activities are discussed.

Coumarins scaffolds as COX inhibitors.

The discovery of COX enzymes has led to a better understanding of inflammation and its related biological pathways. Apart from being related to inflammation and pain, it has also been associated with cancer and neuropsychiatric diseases such as schizophrenia. Proverbially speaking, study of these enzymes has been crucial as they happen to "have fingers in many pies". Non-steroidal anti-inflammatory drugs (NSAID) that act specifically as COX-2 inhibitors have been known for a while; however these are also associated with severe side effects such as cardiac problems. Several heterocylic molecules have been tested for their anti-inflammatory activity specifically as COX-inhibitors. Coumarins also known as benzopyrans are widely found in nature, and are routinely employed as herbal remedies since early days. Over 1300 coumarins have been identified, principally as secondary metabolites in green plants, fungi and bacteria. Recently the use of natural and synthetic coumarins has garnered a lot of attention for their anti-inflammatory activities. In this review we delve further into the study of natural and synthetic coumarins as COX-inhibitors. Although the study is still in its nascent stage, we believe there is scope for a lot of development.

Synthesis of new arylisoxazole-oxindole conjugates as potent antiproliferative agents.

A new series of arylisoxazole-oxindole derivatives (6a-r) were synthesized and evaluated for their antiproliferative activity against human cancer cell lines including non-small cell lung (A549), cervical (HeLa), breast (MCF-7), and prostate (DU-145) cancer cell lines. The synthesized compounds (6a-r) demonstrated excellent to moderate cytotoxicity with IC50 values ranging from 0.82 to 3.69 µm. Some new compounds (6m-r) exhibited profound cytotoxicity better or similar to positive control. More particularly, the compound 6q possesses donating substituent like methoxy group presented at 5-position on D ring exhibited remarkable antiproliferative activity against A-549 (lung cancer) with an IC50 value 0.82 µm. Further studies to determine the mechanistic aspects of these conjugates are under progress.

Synthesis of benzopyran linked pyrrolo[2,1-c][1,4]benzodiazepines as DNA-binding and potential anticancer agents.

A series of twelve benzopyran linked pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have been synthesized. They exhibit significant DNA-binding activity and excellent cytotoxic activity against various human cancer cell lines.