Novel -Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations.

Significant advancements have been made in the domain of targeted anticancer therapy for the management of malignancies in recent times. VEGFR-2 is characterised by its pivotal involvement in angiogenesis and subsequent mechanisms that promote tumour cells survival. Herein, novel -arylmethyl-aniline/chalcone hybrids were designed and synthesised as potential anticancer and VEGFR-2 inhibitors.

New phenothiazine conjugates as apoptosis inducing agents: Design, synthesis, In-vitro anti-cancer screening and I-radiolabeling for in-vivo evaluation.

Phenothiazines (PTZs) are a group of compounds characterized by the presence of the 10H-dibenzo-[b,e]-1,4-thiazine system. PTZs used in clinics as antipsychotic drugs with other diverse biological activities. The current aim of the study is to investigate and understand the effect of potent PTZs compounds using a group of In-vitro and In-vivo assays.

2,4-Diaryl-pyrimido[1,2-a]benzimidazole derivatives as novel anticancer agents endowed with potent anti-leukemia activity: Synthesis, biological evaluation and kinase profiling.

Acute myeloid leukemia (AML) stands as one of the most aggressive type of human cancer that can develop rapidly and thus requires immediate management. In the current study, the development of novel derivatives of pyrimido[1,2-a]benzimidazole (5a-p) as potential anti-AML agents is reported. The prepared compounds 5a-p were inspected for their in vitro anti-tumor activity at NCI-DTP and subsequently 5h was selected for full panel five-dose screening to assess its TGI, LC and GI values.

Novel hydrazone-isatin derivatives as potential EGFR inhibitors: Synthesis and in vitro pharmacological profiling.

Merging isatin and arylhydrazone moieties constitutes an efficient strategy to access new potential anticancer derivatives. Consequently, 14 hydrazone-isatin derivatives were synthesized and evaluated for their antiproliferative activity against the NCI-60 cancer cell line panel. A kinase assay demonstrated that compound VIIIb inhibited the epidermal growth factor receptor (EGFR), which was confirmed by docking studies, molecular dynamics, and binding free energy calculations.

3-Substituted-2,3-Dihydrothiazole as a promising scaffold to design EGFR inhibitors.

The overexpression of EGFR has been recognized as the driver mechanism in the development of several human malignancies and the clinical use of EGFR inhibitors currently constitutes the standard of care for a wide range of malignancies, including colorectal cancer. However, the clinical efficacy of EGFR targeted inhibitors is limited by the development of intrinsic or acquired resistance, requiring the discovery of new compounds with different structural characteristics from those already developed. In this context, we explored the replacement of the aminoquinazoline pharmacophore of several FDA-approved EGFR inhibitors by its bioisosteric hydrazinothiazole moiety.

Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates - was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds , - and showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound.

Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, study, and exploratory clinical appraisal.

The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment.

Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer.

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates ( and ) was designed and synthesised. The anticancer activity for compounds (, and ) was measured against NCI-55 human cancer cell lines. Compound was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels.

Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations.

In the current medical era, human health is experiencing numerous challenges, particularly the human malignancies. Therefore, the therapeutic arsenal for these malignancies is to be inexorably enhanced with new treatments that target tumor cells in a selective manner. In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors.

Novel piperazine-chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation.

New piperazine-chalcone hybrids and related pyrazoline derivatives have been designed and synthesised as potential vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The National Cancer Institute (NCI) has selected six compounds to evaluate their antiproliferative activity against 60 human cancer cells lines. Preliminary screening of the examined compounds indicated promising anticancer activity against number of cell lines.

Development of 2-oindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells.

Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive target for anticancer drug discovery. In this manner, the present studies developed a series of novel isatin-indole conjugates ( and ) as potential anticancer Bcl2 and BclxL inhibitors.

Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies.

Novel hybrids of pyridazine-pyrazoline were synthesized aiming to develop new antiproliferative candidates. All compounds were submitted to the National Cancer Institute (NCI), USA, and many were proved to have significant antiproliferative activity. In addition, in vitro studies of the epidermal growth factor receptor (EGFR) inhibition showed that compounds IXn, IXg, IXb and IXl exhibited excellent inhibitory effect (IC = 0.

3-Methylthiazolo[3,2-a]benzimidazole-benzenesulfonamide conjugates as novel carbonic anhydrase inhibitors endowed with anticancer activity: Design, synthesis, biological and molecular modeling studies.

Herein we describe design and synthesis of different series of novel small molecules featuring 3-methylthiazolo[3,2-a]benzimidazole moiety (as a tail) connected to the zinc anchoring benzenesulfonamide moiety via ureido (7), enaminone (12), hydrazone (14), or hydrazide (15) linkers. The newly prepared conjugates have been screened for their inhibitory activities toward four human (h) carbonic anhydrase (CA, EC 4.2.

Inclusion of a 5-fluorouracil moiety in nitrogenous bases derivatives as human carbonic anhydrase IX and XII inhibitors produced a targeted action against MDA-MB-231 and T47D breast cancer cells.

A new series of pyrimidine derivatives as human carbonic anhydrases (CA, EC 4.2.1.

Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents.

Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chemical framework.

Synthesis, In-vivo and In-vitro Anti-inflammatory Evaluation of some Novel Coumarin Derivatives.

Background: Synthetic coumarin derivatives had attracted considerable attention for their broad spectrum of biological and pharmacological activities such as; anticoagulant, antiviral, antibacterial, antitumor and anti-inflammatory activities especially as COX inhibitors.

Objective: Synthesis of some new coumarin esters using different benzoyl chloride derivatives. The benzoyl chloride derivatives were selected to have different hydrophobic groups and this aims to increase the lipophilicity of the final compounds hoping to increase the bioavailability and thus improve the anti-inflammatory activity.

Synthesis and Evaluation of Some Dibromoquinazoline-sulphonamide Hybrids and some Schiff´s Base Analogs for their Cytotoxic Activity.

Background: Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity.

Objective: In this work our aim is to develop novel, safe and effective anticancer agents.

Salmeterol Xinafoate.

Salmeterol xinafoate is a potent and a long-acting β2-adrenoceptor agonist. It is prescribed for the treatment of severe persistent asthma and chronic obstructive pulmonary disease. Different methods were used to prepare (R)-(-)-salmeterol such as: mixing a sample of 4-benzyloxy-3-hydroxymethyl-ω-bromoacetophenone with sodium lauryl sulfate and the mixture was added to the microbial culture of Rhodotorula rubra, treatment of p-hydroxyacetophenone with Eschenmoser's salt and carbonate exchange resin followed by a sequence of supported reagents and scavenging agents or via Rh-catalyzed asymmetric transfer hydrogenation.

Anti-inflammatory screening and molecular modeling of some novel coumarin derivatives.

Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 1-11 was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. Compounds 2, 3, 4 and 9 showed significant (p < 0.

Molecular design of small organic molecules based on structural information for a conformationally constrained peptide that binds to G-CSF receptor.

Based on structural information for a peptide (P8-2KAQ) that binds to granulocyte-colony stimulating factor receptor (G-CSFR), small ligands with a biaryl scaffold were designed and their binding affinities were evaluated.