Aakash Deep

Cabazitaxel: A Novel Drug for Hormone-Refractory Prostate Cancer

Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can penetrate blood brain barrier (BBB). The FDA granted fast track designation to this drug in November 2009 and thereafter, new drug application submission was done in March 2010. Priority review to this drug was granted in April 2010 and finally in July 2010 it was approved by FDA. It is available in the form of injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use by the diluents supplied along with the injection. It is a second-line drug and has proven to be effective in patients experiencing docetaxel based treatment failure.

Synthesis and preliminary therapeutic evaluation of copper nanoparticles against diabetes mellitus and -induced micro- (renal) and macro-vascular (vascular endothelial and cardiovascular) abnormalities in rats

The current study synthesized and investigated the effect of low-dose copper nanoparticles (CuNPs) against diabetes mellitus (streptozotocin, 50 mg kg−1, i.p., once) and -induced experimental micro- (nephropathy) and macro-vascular (cardio and endothelium) complications. Diabetes mellitus (DM)-induced vascular abnormalities were revealed by the reduction in acetylcholine-induced endothelium-dependent relaxation, the decrease in aortic and serum nitrite/nitrate concentration, increased CKMB, LDH, SGOT/SGPT, serum creatinine, and blood urea nitrogen, and the induction of proteinuria and oxidative stress. However, treatment with low-dose CuNPs (1 mg kg−1, p.o. 4 weeks) after streptozotocin administration reduced serum glucose concentration. Moreover, CuNPs had shown a partial but significant prevention of cardio-vascular structural and functional abnormalities in diabetic rats. Increased bioavailability of NO in the endothelium and reduction in oxidative stress might be the possible mechanisms involved for the protective role of CuNPs against diabetes-induced micro- and macro-complications.

Synthesis, Antimicrobial and Anticancer Evaluation of 2-Azetidinones Clubbed with Quinazolinone

A novel series of 2-azetidinones clubbed with quinazolinone was synthesized using anthranilic acid. All the synthesized compounds were evaluated for their antimicrobial activity against two Gram positive bacterial strains (Bacillus subtilis and Staphylococcus aureus), one Gram negative bacterial strain (Escherichia coli) and two fungal strains (Candida albicans and Aspergillus niger). All the synthesized compounds were also screened for their anticancer activity against human breast cancer cell line, MCF-7. Results of antimicrobial and anticancer study indicate that compounds 12 and 5 (IC50 = 49.52 μM) are the most potent antimicrobial and anticancer agents, respectively.

Inhibitor designing, virtual screening, and docking studies for methyltransferase: A potential target against dengue virus.

Aim: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. Introduction: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. Materials and Methods: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. Results: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. Conclusion: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation.

Synthesis, characterization and antimicrobial evaluation of novel derivatives of isoniazid

In the present investigation, a series of new Mannich bases were prepared by the reaction of 2-ethoxybenzaldehyde with isoniazid to form acid hydrazone (3a). Further, C-Mannich bases of the above acid hydrazone were prepared by aminomethylation with formaldehyde and substituted secondary amines (3b–3k). The structures of newly synthesized compounds were evaluated by elemental analyses and spectral (IR, 1H NMR, 13C NMR) studies. All the synthesized compounds were evaluated for their antimicrobial activity. Amoxicillin was used as a standard drug for antibacterial activity while Nystatin was used as a standard drug for antifungal activity. Preliminary pharmacological evaluation revealed that the compound (3f, 3i, 3j, 3k) showed better performance against Bacillus subtilis,Staphylococcus aureus,Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Candida gabrata. The result demonstrates the potential and importance of developing new mannich bases which would be effective against resistant bacterial and fungal strain.

4-Thiazolidinone derivatives: synthesis, antimicrobial, anticancer evaluation and QSAR studies

A series of 4-thiazolidinone derivatives (1–18) was synthesized and tested in vitro for its antimicrobial and anticancer potential. Synthesized compounds were found to be 5 more potent antimicrobial agents than anticancer agents. Anticancer screening results indicated that compound 13 (IC50 = 15.18 μM) was the most active anticancer agent and was more potent than the standard drug, carboplatin (IC50 > 100 μM). Antimicrobial activity results indicated that 14 was the most active antimicrobial agent (pMICec = 2.14 μM) and may serve as an important lead for the discovery of novel antimicrobial agents. The QSAR studies indicated that the antibacterial and antifungal activities of the synthesized derivatives against different microbial strains were governed by lipophilic parameter, log P, topological parameter, κα3 and electronic parameters cos E and Nu. E.

Benzothiazole Derivatives as Potential Anti-Infective Agents

BACKGROUND Severity of microbial infections and escalating resistance towards antibiotics has created a deep necessity for discovery of novel anti-infective agents. Heterocyclic chemistry of benzothiazole has become one of the most prolific areas in the field of drug discovery and development that has attracted great attention in recent time due to its increasing importance in the field of pharmaceuticals. METHOD The importance of benzothiazole and derivatives as potential antimicrobial agents has been well established and a large number of papers have been published in this regard. RESULT The present communication is an earnest attempt to review the chemistry, synthetic aspects including click chemistry and antimicrobial activities of benzothiazole derivatives reported in recent scientific literature. CONCLUSION The scientific information of this manuscript may be worthwhile in encouraging the prospective researchers working on this heterocyclic scaffold.

Pyrimidine Derivatives as Potential Agents Acting on Central Nervous System

Pyrimidine and its derivatives are present in many of the bioactive aromatic compounds that are of wide interest because of their diverse biological and clinical applications. The utility of pyrimidines as synthon for various biologically active compounds has given impetus to these studies. The review article aims to review the work reported on pharmacological activities of central nervous system (CNS) such as anticonvulsant and antidepressant, which created interest among researchers to synthesize variety of pyrimidine and their derivatives. The present study shows, objective of the work can be summarized as pyrimidine derivative constitute an important class of compounds for new drug development. These observations have been given novel idea for the development of new pyrimidine derivative that possess varied biological activities. This article aims to review the recent works on pyrimidine moiety together with the biological potential during the past year.

Thiophene Scaffold as Prospective Central Nervous System Agent: A Review.

BACKGROUND Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. METHOD Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. RESULT Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin-dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. CONCLUSION The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived.

Synthesis, Antimicrobial, Anticancer Evaluation of 2-(aryl)-4- Thiazolidinone Derivatives and their QSAR Studies

A new class of 4-thiazolidinones clubbed with quinozolinone nucleus has been synthesized. The title compounds were screened for their in vitro antimicrobial and anticancer potentials. Results of antimicrobial and anticancer study revealed that compounds 7 (pMICam = 1.69 μM/ml) and 2 (IC50 = 12.83 μM) were found to be the most potent antimicrobial and anticancer agents respectively. QSAR studies indicated that antimicrobial activity of synthesized 4-thiazolidinone derivatives was governed by the electronic parameters, dipole moment (μ), energy of highest occupied molecular orbital (HOMO), lipophilic parameter, log P and topological parameter, valence third order molecular connectivity index ((3)χ(v)).