M. Mumtaz Alam

Pyrazolines: A Biological Review

Pyrazoline is an important five membered nitrogen heterocycle, which has been extensively researched upon. The ring is quite stable and has inspired chemists to carry out various structural variations in the ring. This has propelled the development of distinct pyrazolines with an array of pharmacological activities viz. anti-inflammatory, analgesic, antimicrobial, anticancer, antidepressant etc. The review aims at highlighting this pharmacological diversity of pyrazolines. The review is a gist of latest work done describing the pharmacological aspects and potential of pyrazoline ring.

Therapeutic evolution of benzimidazole derivatives in the last quinquennial period

Benzimidazole, a fused heterocycle bearing benzene and imidazole has gained considerable attention in the field of contemporary medicinal chemistry. The moiety is of substantial importance because of its wide array of pharmacological activities. This nitrogen containing heterocycle is a part of a number of therapeutically used agents. Moreover, a number of patents concerning this moiety in the last few years further highlight its worth. The present review covers the recent work published by scientists across the globe during last five years.

Recent Updates on Biological Activities of Oxadiazoles

Among the plethora of heterocyclic nucleus discovered, the oxadiazoles have also been explored extensively. The oxadiazole structure has been demonstrated to bear important biological activities such as anti-cancer, antiinflammatory, anti-tuberculosis, anti-malarial and anti-schistosomiasis etc. The presence of oxadiazole motifs in diverse types of compounds proves its importance in the field of medicinal chemistry. This review is complementary to earlier reviews and covers recent updates of various pharmacological aspects of oxadiazoles. To help the reader better know the context for these approaches, a summary of various aspects of background of related topic is presented.

Neuroprotective effect of naphtha[1,2-d]thiazol-2-amine in an animal model of Parkinson's disease

Increased oxidative stress has been implicated in the pathogenesis of dopaminergic neurodegeneration leading to the development of Parkinsons disease. In this study, we investigated whether naphtha[1,2-d]thiazol-2-amine (NTA) may ameliorate haloperidol-induced catalepsy and oxidative damage in mice brain. Haloperidol-induced catalepsy was measured with the standard bar test. The extent of oxidative stress has been evaluated by measuring levels of MDA, GSH and activities of antioxidant enzymes (SOD and GSH-Px) from brain homogenate. Haloperidol treatment significantly induced the catalepsy as observed from increased descent time measured in the bar test. Pretreatment with NTA significantly reduced the catalepsy induced by haloperidol in a dose-dependent manner. The elevated level of MDA in haloperidol-treated mice was significantly decreased by NTA pretreatment. The decreased level of GSH as well as SOD and GSH-Px activities in haloperidol-treated mice were significantly increased by NTA pretreatment. NTA reduces the oxidative stress allowing recovery of detoxifying enzyme activities and controlling free radical production, suggesting a potential role of the drug as an alternative/adjuvant drug in preventing and treating the neurodegenerative diseases, such as Parkinsons disease.

The therapeutic journey of pyridazinone.

Pyridazinones have drawn a substantial attention within the field of research analysis and development. The moiety is a subject matter of intensive research because of its wide spectrum of biological activities and therapeutic applications. The synthesis of pyridazinone and investigation of their chemical and biological activities have gained additional importance in recent years. In this review, we have compiled and discussed various biological and therapeutic potential of pyridazinone derivatives.

Pharmacophore model generation and 3D-QSAR analysis of N-acyl and N-aroylpyrazolines for enzymatic and cellular B-Raf kinase inhibition

A successful 3D-QSAR study has been performed for amino-substituted N-acyl and N-aroylpyrazolines as B-Raf kinase inhibitors by means of a common five-point pharmacophore model. In this study, highly predictive 3D-QSAR models have been developed for B-Raf kinase inhibition and pERK inhibition using AADRR-2 and AADRR-6 hypothesis, respectively. The best models showed statistically outstanding values of 0.97, 0.95 and 0.91, 0.87 for r2 and q2 for AADRR-2 and AADRR-6 hypothesis, respectively. The validation of the PHASE model was done by dividing the dataset into training and test set. From the QSAR model, it can implicated that electron-withdrawing and hydrophobic groups are not advantageous for both enzymatic and cellular activities. However, H-bond donor characteristic is favorable for cellular inhibition and unfavorable for enzymatic inhibition. Based on the findings of the 3D-QSAR study, novel and promising compounds for B-Raf kinase inhibition can be synthesized.

Novel hybrid-pyrrole derivatives: their synthesis, antitubercular evaluation and docking studies

Using novel hybrid molecules for the treatment of tuberculosis is one of the latest approaches. Keeping this concept in mind, thirty two hybrid compounds were synthesized, with pyrrole as one of the moieties, clubbed to coumarin, ibuprofen and isoniazid. The compounds were evaluated against Mycobacterium tuberculosis H37Rv strain. Compounds 7e and 8e exhibited MIC of 3.7 and 5.10 μg mL−1 and growth inhibition of 95% and 92%, respectively. These compounds were also active against single drug resistant bacterial strains. The compounds were devoid of cytotoxicity when tested against Vero African green monkey kidney cell line. Docking study was carried out on enoyl acyl carrier protein enzyme to provide some understanding into the mechanism of action of these compounds.

Pharmacophore based virtual screening, synthesis and SAR of novel inhibitors of Mycobacterium sulfotransferase

A planned 3D-pharmacophore mapping was carried out on the basis of chemical features associated with known Stf0 inhibitors. Four models (model 1-4) were obtained after GASP (Genetic Algorithm Similarity Program) refinement of seven models (D-1 to D-7) generated by using DISCOtech. The selected GASP model-1 has two hydrogen bond acceptor, two hydrogen bond donor and four hydrophobic points. This model was used for virtual screening (VS) of large public databases along with in house generated knowledge base database. VS followed by docking of selected compounds on Stf0 active site was carried and pose analysis done. Seven hits were identified after all the computational studies, of which 2 hits were synthesized along with their analogs and evaluated for antitubercular activity. IH-45 was found promising after in vitro assay.

Malaria: Hitches and Hopes

Malaria, a devastating infectious disease caused by parasites of Plasmodium genera is transmitted from person to person through bites of infected mosquitoes. It generally traps underdeveloped nations with poor infrastructure and high population density. It has attracted considerable attention from academic institutions, pharmaceutical industries and government agencies but the efforts to eradicate this threat face a number of technical, economic, financial and institutional hurdles. In the absence of clinically proven vaccines to combat malaria, chemotherapy continues to be the best available option, although it suffers from a big loophole of resistance. Emergence of resistance is associated with the two phases of Plasmodiums life cycle: asexual in humans and sexual in mosquito, which are intricate to target simultaneously. Consequently, the search for novel antimalarial agents is a never-ending task for scientists and chemists. This review aims at highlighting the currently used antimalarial agents, targets for the therapy and present scenario in the development of new antimalarial drugs to combat this global problem.

Synthesis of Hybrids of Dihydropyrimidine and Pyridazinone as potential Anti-Breast Cancer Agents

BACKGROUND Different 3-aroylpropionic acids and dihydropyrimidine hydrazine derivatives were condensed together to yield a series of dihydropyrimidine and pyridazinone hybrids (5a-u). OBJECTIVE This was done in order to develop therapeutic agents for the treatment of breast cancer with improved Cycloxygenase-2 (COX-2) selectivity. In-vitro anticancer evaluation for these compounds was done against human breast cancer cell lines (MCF-7, MDA-MB-231) and normal human keratinocytes (HaCaT). CONCLUSION Amongst all the developed analogs, compound 5l emerged as the most potent agent against both these cell lines with IC50 values of 3.43 and 2.56 µM respectively. The synthesized compounds were also evaluated for COX-2 selectivity. To observe the binding pattern of the compounds with COX-2, a docking study was performed using PDB ID: 1CX2.