Limonoids serve as vital secondary metabolites. Citrus limonoids show a wide range of pharmacological potential. As a result of which limonoids from citrus are of considerable research interest. Identification of new therapeutic molecules from natural origins has been widely adopted as a successful strategy in drug discovery. The current work mainly focused on the high-throughput computational exploration of the antiviral potential of three vital limonoids i.e. Obacunone, Limonin, and Nomilin against spike proteins of SARS CoV-2 (PDB:6LZG), Zika virus NS3 helicase (PDB:5JMT), Serotype 2 RNA dependent RNA polymerase of dengue virus (PDB:5K5M). Herein we report the molecular docking, MD simulation studies of nine docked complexes, and density functional theory of selected limonoids. The results of this study indicated that all three limonoids have good molecular features but out of these three obacunone exerted satisfactory results for DFT, docking, and MD simulation study.

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Background: Cancer is the leading cause of death in the current decade. With the advancement in scientific technologies various treatments had been introduced but they suffer from numerous side effects. The root cause of cancer is alteration in the cell cycle which generates cancerous cells. Development of new lead which specifically target cancerous cells is needed to reduce the side effect and to overcome multidrug resistance. Objective: Design and development of anticancer leads targeting colchicine site of microtubules using structurally screened phytofragments is the primary objective of this work. Material and methods: Bioactive fragments of phytoconstituents were identified from a large dataset of phytochemicals. The identified phytofragments were used to design structures which were screened for virtual interactions with colchicine site of microtubules. Selected set of designed molecules was further screened for drug like properties and toxicity. The designed molecules which surpassed virtual filters were then synthesized, characterized and further screened for anticancer potential against HEPG2 liver cancer cellline. Result: A novel series of chalcones was designed by phytofragment based drug design. The synthesized compounds showed profound anticancer activity comparable to standard, 5-fluoro uracil. In the present communication, rational development of anticancer leads targeting colchicine site of microtubules has been done by integrating pocket modeling and virtual screening with synthesis and biological screening. Conclusion: In this present work, we found that compound S4 and S3 showed specific interaction with colchicine site of microtubules and desirable anticancer activity. Further optimization of the lead could yield drug like candidate with reduced side effects and may overcome multidrug resistance.

Background: Cysteine protease and DHODH enzyme were identified as potential target and for synthesized compound which revealed binding interaction and confirmation from docking study. Development of new lead which specifically targeting cysteine protease and DHODH enzyme can be able to reduce the side effect and to overcome multidrug resistance. Objectives: Design and development of antimalarial agents by targeting cysteine protease and DHODH (Dihydroorotate dehydrogenase) enzyme by structure based drug design. Materials and Methods: In present work, rational development of antimalarial agents by targeting cysteine protease and DHODH has been done by integrating binding confirmation from virtual analysis and synthetic procedures. Result: A novel series of dihydroisoquinolines were designed by structure based drug design. Large compounds of dataset were screened for molecular docking study and subsequently all molecules were screened for drug like properties and toxicity study prior to synthesis. The designed molecules which analysed by virtual screening were synthesized, characterized and finally screened for antimalarial activity by performing bioassay. Synthesized compounds were showed greater antimalarial activity in terms percent inhibition. Conclusion: In this work, compound A1,A5,A6,A9 showed desirable inhibitory activity toward targets in terms of percentage and also specific hydrogen binding interaction with those targets. Further optimization in leads able to yield drug like candidate and it may able to overcome multidrug resistance.

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.