Structure activity relationship for anticancer activities of spirooxindole derivatives: A comprehensive review.

Cancer remains one of the leading causes of mortality worldwide, necessitating the continuous search for novel therapeutic agents. Spirooxindole derivatives have recently emerged as a class of compounds with significant potential for cancer treatment owing to their diverse pharmacological activities and unique structural features. The structural diversity of spirooxindole derivatives enables a wide range of modifications, facilitating optimization of their pharmacokinetic and pharmacodynamic properties.

Indole Derivatives as New Structural Class of Potent and Antiproliferative Inhibitors of Monocarboxylate Transporter 1 (MCT1; SLC16A1).

The solute carrier (SLC) monocarboxylate transporter 1 (MCT1; SLC16A1) represents a promising target for the treatment of cancer; however, the MCT1 modulator landscape is underexplored with only roughly 100 reported compounds. To expand the knowledge about MCT1 modulation, we synthesized a library of 16 indole-based molecules and subjected these to a comprehensive biological assessment platform. All compounds showed functional inhibitory activities against MCT1 at low nanomolar concentrations and great antiproliferative activities against the MCT1-expressing cancer cell lines A-549 and MCF-7, while the compounds were selective over MCT4 (SLC16A4).

Evaluation of oxindole derivatives as a potential anticancer agent against breast carcinoma cells: In vitro, in silico, and molecular docking study.

In this study we have performed the in vitro anticancer activity of spiro oxindole derivatives against MCF-7 (human Adreno carcinoma) and MDA-MB-231 (triple negative breast cancer) cell lines to propose a possible role of these derivatives in the treatment of cancer. Compound 6, which has an N-benzyl substitution with a chloro group on the indolin-2-one scaffold, had the most potent activity against MCF-7 (3.55 ± 0.

Applications of Nanotechnology-based Approaches to Overcome Multi-drug Resistance in Cancer.

Cancer is one of the leading causes of death worldwide. Chemotherapy and radiation therapy are the major treatments used for the management of cancer. Multidrug resistance (MDR) is a major hindrance faced in the treatment of cancer and is also responsible for cancer relapse.

Monocarboxylate transporter 1 and 4 inhibitors as potential therapeutics for treating solid tumours: A review with structure-activity relationship insights.

Development of multidrug resistance (MDR) is one of the major causes leading to failure of cancer chemotherapy and radiotherapy. Monocarboxylate transporters (MCTs) MCT1 and MCT4, which are overexpressed in solid tumours, play a very important role in cancer cell survival and proliferation. These lactate transporters work complimentarily to drive lactate shuttle in tumour cells, which results in maintenance of H ion (pH) balance necessary for their survival.

Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a vital enzyme involved in the synthesis of guanine nucleotides. IMPDH catalyzes a crucial step of converting IMP into XMP that is further converted into GMP. Microbial infections rely on the rapid proliferation of bacteria, and this requires the rate-limiting enzyme IMPDH to expand the guanine nucleotide pool and hence, IMPDH has recently received lots of attention as a potential target for treating infections.

Cancer cell fusion: a potential target to tackle drug-resistant and metastatic cancer cells.

Cell fusion is an integral, established phenomenon underlying various physiological processes in the cell cycle. Although research in cancer metastasis has hypothesised numerous molecular mechanisms and signalling pathways responsible for invasion and metastasis, the origin and progression of metastatic cells within primary tumours remains unclear. Recently, the role of cancer cell fusion in cancer metastasis and development of multidrug resistance (MDR) in tumours has gained prominence.

Design, synthesis and biological evaluation of Helicobacter pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) inhibitors. Further optimization of selectivity towards HpIMPDH over human IMPDH2.

Inosine 5'-monophosphate dehydrogenase (IMPDH, EC 1.1.1.

Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors.

Background & Objective: Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori.

Identification of selective inhibitors of Helicobacter pylori IMPDH as a targeted therapy for the infection.

Helicobacter pylori (H. pylori), the major cause of several gastric disorders has been recognied as a type I carcinogen. By virtue of resistance developed by H.

Novel chalcone and flavone derivatives as selective and dual inhibitors of the transport proteins ABCB1 and ABCG2.

During cancer chemotherapy, certain cancers may become cross-resistant to structurally diverse antineoplastic agents. This so-called multidrug resistance (MDR) is highly associated with the overexpression of ATP-binding cassette (ABC) transport proteins. These membrane-bound efflux pumps export a broad range of structurally diverse endo- and xenobiotics, including chemically unrelated anticancer agents.

Water-mediated intermolecular interactions in 1,2-O-cyclohexylidene-myo-inositol: a quantitative analysis.

The syntheses of new myo-inositol derivatives have received much attention due to their important biological activities. 1,2-O-Cyclohexylidene-myo-inositol is an important intermediate formed during the syntheses of certain myo-inositol derivatives. We report herein the crystal structure of 1,2-O-cyclohexylidene-myo-inositol dihydrate, CHO·2HO, which is an intermediate formed during the syntheses of myo-inositol phosphate derivatives, to demonstrate the participation of water molecules and hydroxy groups in the formation of several intermolecular O-H.

The combination of quinazoline and chalcone moieties leads to novel potent heterodimeric modulators of breast cancer resistance protein (BCRP/ABCG2).

During the last decade it has been found that chalcones and quinazolines are promising inhibitors of ABCG2. The combination of these two scaffolds offers a new class of heterocyclic compounds with potentially high inhibitory activity against ABCG2. For this purpose we investigated 22 different heterodimeric derivatives.

Design of inhibitors of BCRP/ABCG2.

BCRP/ABCG2, a second member of ABC transporter subclass G, has been shown to be overexpressed in several solid tumors, acute myelogenous leukemia and chronic myeloid leukemia. A variety of chemically unrelated anticancer drugs have been found to be transported by ABCG2 leading to their lower intracellular accumulation and hence causing chemoresistance. Until now several efforts have been taken to identify potent and selective inhibitors of ABCG2.

Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation.

Overcoming multidrug resistance (MDR) in cancer is a major challenge and efforts are on-going to develop inhibitors against the most characterized and ubiquitous MDR transporters: P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1) and breast cancer resistance protein (BCRP). Recently reported, two 4-anilinoquinazolines (compounds 1 and 2), demonstrate potential MDR reversal activity against BCRP and to a lesser extent, P-gp. In this work, we formulated the compounds as polymeric nanoparticles (NPs) and assessed their MDR inhibitory activity in relevant BCRP and P-gp over-expressing cell line models.

Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity.

Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the superfamily of ATP binding cassette (ABC) transporters. Characteristic of some of these transporter proteins is the transport of a variety of structurally unrelated substances against a concentration gradient by using the energy of ATP hydrolysis. ABCG2 has been found to confer multidrug resistance (MDR) in cancer cells.

Investigation of quinazolines as inhibitors of breast cancer resistance protein (ABCG2).

Chemotherapy is one of the major forms of cancer treatment. Unfortunately, tumors are prone to multidrug resistance leading to failure of treatment. Breast cancer resistance protein (BCRP), the second member of ABC transporter subfamily G, has been found to play a major role in drug efflux and hence multidrug resistance.

Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2.

Multidrug resistance (MDR) often leads to a failure of cancer chemotherapy. Breast Cancer Resistance Protein (BCRP/ABCG2), a member of the superfamily of ATP binding cassette proteins has been found to confer MDR in cancer cells by transporting molecules with amphiphilic character out of the cells using energy from ATP hydrolysis. Inhibiting BCRP can be a solution to overcome MDR.

4-Substituted-2-phenylquinazolines as inhibitors of BCRP.

We investigated several 2-phenylquinazolines with different substitutions at position 4 for their BCRP inhibition. Compounds with phenyl ring attached via an amine-containing linker at position 4 were found to be potent inhibitors of BCRP. In general compounds with meta substitution of phenyl ring at position 4 were found to have higher inhibitory effect, compound 12 being the most potent and selective towards BCRP.

Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein.

Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors.