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  1. Synthesis, Biological Evaluation and Molecular Docking Studies of New Pyrazolines as an Antitubercular and Cytotoxic Agents
    Lokesh BVS, Prasad YR, Shaik AB
    Infect Disord Drug Targets, 2019;19(3):310-321.
    PMID: 30556506 DOI: 10.2174/1871526519666181217120626
    BACKGROUND: Many synthetic procedures were reported till date to prepare pyrazoline derivatives. Some have published pyrazolines from different chalcone derivatives in the literature.

    OBJECTIVE: A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro anticancer activity against DU-145 prostate cancer cell lines and all compounds were also screened for molecular docking studies against specific targeted protein domains.

    METHODS: All compounds were screened for potential activity against Mycobacterium tuberculosis H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT cytotoxicity assay.

    RESULTS: Among the series, compound PZT5 with 2", 4"-dichlorophenyl group at 5-position on the pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 µg/mL) and compounds PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against standard pyrazinamide (MIC=3.12 µg/mL) by broth dilution assay. PZT15 and PZT17 with 4"- pyridinyl and 2"-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 µg/mL and 6.0±0.3 µg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized. The molecular docking studies with crystalline structures of enoyl acyl carrier protein reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity. Ligand interaction and binding affinity were estimated using crystal structures of both types of enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to - 19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule. Whereas the binding affinities of six active compounds with crystal structure of other type of enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to - 11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole).

    CONCLUSION: These new pyrazolines would be promising potent inhibitors of drug sensitive and drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate cancer and other prototypes of cancers.

  2. Fulltext Molecular mechanisms underlying the regulation of tumour suppressor genes in lung cancer
    Lee JY, Bhandare RR, Boddu SHS, Shaik AB, Saktivel LP, Gupta G, et al.
    Biomed Pharmacother, 2024 Apr;173:116275.
    PMID: 38394846 DOI: 10.1016/j.biopha.2024.116275
    Tumour suppressor genes play a cardinal role in the development of a large array of human cancers, including lung cancer, which is one of the most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering the underlying mechanisms of alterations of tumour suppressor genes in governing tumourigenesis, as well as resistance to cancer therapies. In spite of the encouraging clinical outcomes demonstrated by lung cancer patients on initial treatment, the subsequent unresponsiveness to first-line treatments manifested by virtually all the patients is inherently a contentious issue. In light of the aforementioned concerns, this review compiles the current knowledge on the molecular mechanisms of some of the tumour suppressor genes implicated in lung cancer that are either frequently mutated and/or are located on the chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone to LOH, revealing a recurrent pattern in lung cancer cases. These loci, including 3p14.2 (FHIT), 9p21.3 (p16INK4a), 10q23 (PTEN), 17p13 (TP53), exhibit a higher susceptibility to LOH due to environmental factors such as exposure to DNA-damaging agents (carcinogens in cigarette smoke) and genetic factors such as chromosomal instability, genetic mutations, DNA replication errors, and genetic predisposition. Furthermore, this review summarizes the current treatment landscape and advancements for lung cancers, including the challenges and endeavours to overcome it. This review envisages inspired researchers to embark on a journey of discovery to add to the list of what was known in hopes of prompting the development of effective therapeutic strategies for lung cancer.
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