Pyrazolopyridine: An efficient pharmacophore in recent drug design and development.

Among the various heterocyclic molecules employed for drug design and discovery, pyrazolopyridine is one of the promising pharmacophores. Pyrazolopyridine is a result of fusion of pyrazole and pyridine rings. The potent pharmacology of pyrazolopyridine may be the synergistic effect of pyrazole and pyridine moieties in a single framework. It has been used in drug design of a wide range of diseases such as anticancer, antimicrobial, anti-inflammatory, and neuroprotection. Cancer has become a common disease among elderly people now a days that might be because of genetic inheritance to some extent, carcinogens, pollution, and some infectious diseases. Whatever may be the reason, cancer is one of the major causes of deaths worldwide. In addition, over-usage and improper usage of antibiotics have led to drug resistance of microbes. Further, inflammation is a cause of various diseases such as arthritis, and other diseases. Thus, proinflammatory kinases are considered as primary target for inhibition of inflammation. In view of this, a work that compiles potent pharmacology of recently reported pyrazolopyridine analogs has been planned. The review is aimed to discuss pharmacology in brief along with structure-activity relationship (SAR). The review would emphasize importance of pyrazolopyridines in future drug design and discovery and may help in design of potent pharmacological agents.

Contribution of N-heterocycles towards anti-tubercular drug discovery (2014-2019); predicted and reengineered molecular frameworks.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, responsible for high death frequency every year all over the world. In this regard, efficient drug-design and discovery towards the prevention of M.tb H37 Rv is of prime concern. Prevention of the infection may include vaccination, and the treatment comprises anti-TB drug regimen. However, the vaccine decreases the risk of tuberculosis infection only to some extent, while drug-resistance limits the efficacy of the existing anti-TB agents. Much improvement has to be achieved to overcome pitfalls such as side effects, high-toxicity, low bioavailability, pharmacokinetics and pharmacodynamics, and hence forth in clinical therapeutics. Amongst heterocyclic compounds, N-heterocycles played a pivotal role in drug-design and discovery. A wide range of microbial diseases are being treated by the N-heterocyclic drugs. The present review comprises description of anti-TB effects of the N-heterocycles such as indoles, triazoles, thiazoles, and pyrazoles. The potent anti-TB activity exerted by the derivatives of these heterocycles is evaluated critically alongside emphasizing structure-activity relationship. Besides, docking studies supporting anti-TB activity is supplemented. Alongside this, based on the potent heterocyclic molecules, the molecular frameworks are designed that would bring about enhanced M. tb H37 Rv inhibitory potencies.

Identification of quinoline-chalcones and heterocyclic chalcone-appended quinolines as broad-spectrum pharmacological agents.

Quinoline derivatives have been reported to possess enticing pharmacological properties. In particular, quinoline-chalcones are identified as promising scaffolds for drug discovery. For a long, the quinoline analogs have been in clinical use for various medical conditions such as cancer inhibitory activity, antibacterial and antifungal, anti-plasmodial, DNA damage inhibitory activity, etc. The number of causalities recorded because of the above-mentioned clinical states is significantly large. Though drug design and discovery is a continuous process all over the world, issues like drug-resistance, low metabolic stability, and long-range side effects are potential hindrances for the continuous use of present pharmacological drugs. In this review work, we focused on the recent drug discovery based on quinoline-chalcones. The work emphasizes the potency of a wide range of quinoline chalcone analogs towards the inhibition of infections caused by the various pathogenic microbes such as bacteria, fungi, plasmodium. Alongside, the quinoline chalcones possessing DNA cleavage properties and cancer cell growth inhibitory properties are also discussed. More importantly, the strongest pharmacological molecules are identified based on the inhibitory properties, cytotoxic values, and pharmacokinetics of synthesized derivatives. Additionally, a structure-activity relationship is established amongst the evaluated molecules. Supplemented by the mechanism of action in few pharmacological activities, the potent activity is also proved by the favorable binding interactions in molecular simulation studies.