Comprehensive computational study in the identification of novel potential cholesterol lowering agents targeting proprotein convertase subtilisin/kexin type 9.

The enzymatic target (PCSK9) is critically involved in the regulation of the lipoprotein metabolism leading to the degradation of low-density lipoprotein receptors (LDLRs) upon binding. Drugs that lower LDL cholesterol (LDL-C) through the inhibition of PCSK9 are useful in the management of hypercholesterolemia which greatly reduces the associated risk of atherosclerotic cardiovascular disease (CVD). In 2015, anti-PCSK9 monoclonal antibodies (mAbs), alirocumab and evolocumab were approved but owing to their high costs their prior authorization practices were impeded, reducing their long-term adherence.

Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis.

Emergence of MDR-TB and XDR-TB led to the failure of available anti-tubercular drugs. In order to explore, identify and develop new anti-tubercular drugs, novel peptidomimetic series of Mtb-peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA.

Novel fatty acid-thiadiazole derivatives as potential antimycobacterial agents.

The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re-establish the importance of naturally abundant fatty acid, a series of fatty acid-thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain.

Transferrin conjugates of antitubercular drug isoniazid: Synthesis and in vitro efficacy.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new anti antitubercular agents. Here, we report the synthesis, characterization and antimycobacterial evaluation of protein-drug conjugates.

Chitosan based copolymer-drug conjugate and its protein targeted polyelectrolyte complex nanoparticles to enhance the efficiency and specificity of low potency anticancer agent.

The effective delivery of low potency anticancer drug is a major challenge. The present study introduces the novel chitosan-polylactic acid (CS-PLA)-drug conjugate and its transferrin receptor targeted polyelectrolyte complex nanoparticles (PEC Nps), encapsulating free drug to increase its potency and specificity. The model drug curcumin (CR) was used and incorporated in this system in both conjugated and encapsulated form.

Synthesis and biological evaluation of novel N' (4-aryloxybenzylidene)- 1H-benzimidazole-2 carbohydrazide derivatives as anti-tubercular agents.

A series of structurally novel, (E)-N'-(4-aryloxybenzylidene)-1H-benzimidazole-2-carbohydrazide derivatives were synthesized by molecular hybridization technique. All these compounds were evaluated against Mycobacterium tuberculosis H37Rv strains using Resazurin Microtiter assay (REMA) method. These compounds showed good antituberculosis activity with minimum inhibitory concentration (MIC) value of the range of 1.

Design, synthesis and antitubercular evaluation of novel series of N-[4-(piperazin-1-yl)phenyl]cinnamamide derivatives.

The analogs of N-[4-(piperazin-1-yl)phenyl]cinnamamide were designed and synthesized by molecular hybridization approach in which part C of the designed molecule was linked through amide and carbamate functionality that improves the physicochemical properties and govern the pharmacokinetic and pharmacodynamic behavior. The systematic modification was done around the Part C to explore the structure activity relationship of antitubercular cinnamamide. All 52 compounds were evaluated for its antitubercular activity against Mycobacterium tuberculosis (M.

Novel 2-(2-benzylidenehydrazinyl)benzo[d]thiazole as potential antitubercular agents.

Molecular hybridization approach was used to synthesize substituted 2-(2-(4-aryl oxy benzylidene) hydrazinyl)benzo thiazole derivatives with 2-hydrazinobenzothiazole and 4-(alicycli/aryl/biaryl/heteroaryl oxy)benzaldehyde as new anti-TB agents. The synthesized compounds, when tested against H37Rv strains of Mtb using Resazurin Microtitre Assay (REMA) method, showed promising activity (MIC 1.35-36.

Novel N'-benzylidene benzofuran-3-carbohydrazide derivatives as antitubercular and antifungal agents.

Tuberculosis constitutes today a serious threat to human health worldwide, aggravated by the increasing number of identified multi-drug resistant strains of Mycobacterium tuberculosis (Mtb), its causative agent, as well as by the lack of development of novel mycobactericidal compounds for the last few decades. A novel series of benzofuran-3-carbohydrazide and its analogs was synthesized and characterized spectroscopically. All the compounds were characterized and screened for in vitro anti-tuberculosis (anti-TB) activity against Mycobacterium tuberculosis H37Rv strains by using resazurin assay utilizing microtiter-plate method (REMA).

Novel 2-(2-(4-aryloxybenzylidene) hydrazinyl)benzothiazole derivatives as anti-tubercular agents.

A series of structurally novel, substituted 2-(2-(4-aryloxybenzylidene) hydrazinyl)benzothiazole derivatives incorporating 2-hydrazinyl benzothiazole and 4-(aryloxy)benzaldehyde were designed and synthesized using molecular hybridization approach. All the synthesized compounds exhibited promising activity (MIC 1.5-29.

Pharmacophore development and docking studies of the hiv-1 integrase inhibitors derived from N-methylpyrimidones, Dihydroxypyrimidines, and bicyclic pyrimidinones.

To elucidate the crucial structural features for the HIV-1 integrase inhibitors, a three-dimensional pharmacophore model was developed based on N-methyl pyrimidones, dihydroxypyrimidines, and bicyclic pyrimidinones derivatives using Phase. N-methyl pyrimidone derivative raltegravir, the first US-FDA approved drug by Merck, belongs to this series. The best-fitted common pharmacophore hypothesis was characterized by two acceptor, two hydrophobic, and two ring features having a correlation coefficient of 0.

Synthesis and evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents.

In an attempt to identify new potential lead as antimicrobial agent, 31 novel chloropyrrole derivatives of aroyl hydrazones and chalcones incorporating common pharmacophore of pyoluteorin derivatives were synthesized. Antimicrobial activity of the synthesized compounds was evaluated using broth dilution technique. Based on biological evaluation data it was observed that activity increases as the number of chlorines on pyrrole core increases.